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  • Psychopharmacology
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 339-345 
    ISSN: 1432-1912
    Keywords: Locus coeruleus ; Dopamine ; Noradrenaline ; Adrenaline ; Veratridine ; Tetrodotoxin ; Push-pull cannula ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the release of endogenous dopamine, noradrenaline and adrenaline in the locus coeruleus, this brain area was superfused with artificial cerebrospinal fluid (CSF) through push-pull cannulae and the release of catecholamines was determined in the superfusate radioenzymatically. Collection of superfusates in time periods of 10 min revealed that release rates of the three catecholamines fluctuated, thus pointing to the existence of ultradian rhythms with following mean periods (minutes per cycle): noradrenaline 52±4, dopamine 37±2, adrenaline 36±2. The rhythm frequency of noradrenaline was significantly lower than the frequencies of dopamine and adrenaline. When the locus coeruleus was superfused with neuroactive drugs, superfusates were collected in time periods of 3 min. Superfusion with tetrodotoxin (1 μmol 1−1) for 12 min elicited a prompt and sustained decrease (−70%) in the release rates of dopamine and adrenaline. The release rate of noradrenaline was also reduced, although to a lesser extent (−40%). Superfusion with veratridine (50 μmol 1−1) led to an immediate and very pronounced enhancement in the release rates of dopamine, noradrenaline and adrenaline. The veratridine-induced increase in catecholamine outflow was decreased strongly by simultaneous superfusion with tetrodotoxin. The findings suggest that the release of endogenous catecholamines in the locus coeruleus fluctuates according to ultradian rhythms. Changes in the release on superfusion with veratridine and tetrodotoxin demonstrate the neuronal origin of the three catecholamines. The observed differences in the release characteristics between noradrenaline on the one hand and dopamine and adrenaline on the other might indicate that noradrenaline is partly released from somatodendritic sites of the noradrenergic cell bodies in the locus coeruleus.
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  • 2
    ISSN: 1432-1106
    Keywords: Eye movement ; Horseradish peroxidase ; Semicircular canals ; Three-neuron arc ; Vestibulo-ocular reflex ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Second-order vestibular neurons form the central links of the vestibulo-oculomotor three-neuron arcs that mediate compensatory eye movements. Most of the axons that provide for vertical vestibulo-ocular reflexes ascend in the medial longitudinal fasciculus (MLF) toward target neurons in the oculomotor and trochlear nuclei. We have now determined the morphology of individual excitatory second-order neurons of the anterior semicircular canal system that course outside the MLF to the oculomotor nucleus. The data were obtained by the intracellular horseradish peroxidase method. Cell somata of the extra-MLF anterior canal neurons were located in the superior vestibular nucleus. The main axon ascended through the deep reticular formation beneath the brachium conjunctivum to the rostral extent of the nucleus reticularis tegmenti pontis, where it crossed the midline. The main axon continued its trajectory to the caudal edge of the red nucleus from where it coursed back toward the oculomotor nucleus. Within the oculomotor nucleus, collaterals reached superior rectus and inferior oblique motoneurons. Some axon branches recrossed the midline within the oculomotor nucleus and reached the superior rectus motoneuron subdivision on that side. Since these neurons did not give off a collateral toward the spinal cord, they were classified as being of the vestibulo-oculomotor type and are thought to be involved exclusively in eye movement control. The signal content and spatial tuning characteristics of this anterior canal vestibulo-oculomotor neuron class remain to be determined.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 97 (1994), S. 404-414 
    ISSN: 1432-1106
    Keywords: Anterior ectosylvian cortex ; Vision ; Audition ; Somesthesis ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modality specificity of neuronal responses to visual, somesthetic and auditory stimuli was investigated in the anterior ectosylvian cortex (AEC) of cats, using single-unit recording techniques. Seven classes of neurons were found, and according to their responsiveness to sensory stimuli regrouped into three categories: unimodal, bimodal and trimodal. Unimodal cells that responded to only one of the three stimulus modalities formed 59% of the units; 30.2% were bimodal, in that they showed a clear increase of neuronal discharges to two of the three stimulus types; 10.8% were defined as trimodal because they responded to all three stimulus modalities. Although the different categories of cells were intermingled within the AEC, indicating a certain degree of overlap between sensory modalities, some clustering of cell types was nonetheless evident. Thus, the somatosensory responsive cells were mainly located in the anterior two-thirds of the dorsal bank of the anterior ectosylvian sulcus. Visually responsive cells were concentrated on the ventral bank of the sulcus, whereas neurons with an auditory response occupied the banks and fundus of the posterior three-quarters of the sulcus. The histological distribution and physiological properties of AEC neurons suggest that this cortical region is a higher-order associative area whose function may be to integrate information from different sensory modalities.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 98 (1994), S. 373-378 
    ISSN: 1432-1106
    Keywords: Otolith ; Utricular nerve ; Vestibulocollic reflex ; Neck flexor motoneuron ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the circuitry between the utricular (UT) nerve and ventral neck motoneurons innervating the longus capitis (LC), a neck flexor muscle, in decerebrate cats. We recorded intracellularly from 63 LC (ipsilateral 37, contralateral 26) motoneurons in C1 and C2 segments. UT nerve stimulation evoked disynaptic, excitatory postsynaptic potentials in all ipsilateral LC motoneurons, and inhibitory postsynaptic potentials that were at least trisynaptic in almost all contralateral LC motoneurons. UT effects on neck motoneurons innervating muscles involved in flexion and lateral turning are similar to the connections between the UT nerve and neck extensor motoneurons. These neuron circuits may play a role in fixing the head and the neck to the body during horizontal linear acceleration.
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  • 5
    ISSN: 1432-1106
    Keywords: Photic responsiveness ; Extrastriate cortex ; Orientation selectivity ; Direction selectivity ; End-stop selectivity ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Responsiveness to slits and pattern stimuli was quantified in a total of 68 cells sampled in the posterior extreme of the lateral suprasylvian (PS) cortex as response indices. The cells were studied in relationship to their locations in several subareas of the PS cortex, including areas 19 (n=15) and 21a (n=32) and the posteromedial lateral suprasylvian cortex (PMLS; n=21). These subareas were identified based on retrograde labelling from area 17 and also supplemented with photic responsiveness. This analysis revealed that each cortical area contains cells expressing different combinations of stimulus features. Area 19 contained two major groups of cells: (1) those with strong end-stop selectivity combined with moderate orientation or direction selectivity, and (2) those with weak end-stop selectivity combined with strong orientation selectivity. The groups of cells with strong or moderate orientation selectivity showed a strong preference for stripe over visual noise patterns and relatively large modulatory responses to motion of individual stripes. The PMLS contained one major group of cells with strong end-stop and direction selectivities and with poor orientation selectivity. They also showed stronger preference for visual noise than cells in the other cortical areas and rather weak modulatory responses. Area 21a contained only one group of cells with strong orientation selectivity and length summation property rather than end-stop selectivity, and they also lacked direction selectivity. These cells exhibited a strong preference for stripe patterns and moderate or weak modulatory responses. Altogether, these findings indicate that each cortical area is specialized in expressing different stimulus features. The two groups of cells in area 19 may encode the position and motion of discontinuous visual elements such as corners and line ends and continuous elements such as lines and edges. PMLS cells may encode the motion of single elements or associated motion of multiple discontinuous elements such as textures and backgrounds. Area 21a cells may specifically encode the orientation of long, continuous elements such as lines and edges. In support of this view, two types of statistical analyses demonstrated that the combinations of the response properties expressed in individual PS cells are highly correlated with their locations in cortical areas and that the anatomical locations of individual PS cells are reliably predicted from the sets of response indices expressed in these cells.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 99 (1994), S. 277-288 
    ISSN: 1432-1106
    Keywords: Classical conditioning ; Red nucleus ; Excitatory postsynaptic potentials ; Corticorubral synapses ; Sprouting ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was performed to clarify whether or not structural plasticity of synaptic connections underlies classical conditioning mediated by the red nucleus (RN) in the cat. Conditioned forelimb flexion is established by pairing electrical conditioned stimuli (CS), applied to corticorubral fibers at the cerebral peduncle (CP), with a forelimb skin shock (the unconditioned stimulus, US), but not by applying the CS alone or by pairing the CS and US at random intervals. In our previous study, it was shown that the firing probability of rubrospinal neurons (RN neurons) in response to the CS was well correlated with acquisition of the conditioned forelimb flexion and that the primary site of neural change underlying establishment of the conditioned forelimb flexion was suggested to be at corticorubral synapses. In the present study, we investigated corticorubral excitatory postsynaptic potentials evoked by CP stimulation (CP-EPSPs), in order to identify the neuronal mechanism underlying establishment of classical conditioning. In normal cats, CP-EPSPs had a typical slow-rising phase, which has been attributed to the distal location of corticorubral synapses on the dendrites of RN neurons. In contrast, in animals that received paired conditioning, subsequent CP stimulation evoked potentials with a fast-rising time course. In control groups of cats that received CS alone, CS randomly paired with the US, or only the same surgical operations as the conditioned animals, most of the CP-EPSPs displayed slow-rising EPSPs that similar to those observed in normal cats. The mean time from onset to peak of the potentials in the conditioned animals was significantly shorter than that seen in other groups. Therefore, the appearance of a fast-rising potential correlates well with acquisition of the conditioned forelimb flexion. The amplitude of the fast-rising potential was gradually changed with stimulus intensity. It had a short onset latency following CP stimulation (0.9 ms), which was similar to that of the slow-rising EPSP in normal cats. It followed high-frequency stimulation up to 100 Hz. These results suggest that the newly appearing, fast-rising potential was a monosynaptically evoked EPSP. Fast-rising EPSPs were also induced by stimulation of the sensorimotor cortex (SM). Since the SM-EPSP was occluded by the CP-EPSP, the SM cortex is, at least in part, a likely source of fast-rising EPSPs. Fast-rising SM-EPSPs were also observed at the unitary level. The SM-EPSPs in the conditioned animals exhibited somatotopical representation in their cortical origin, as has been described in normal cats. The electrotonic length was calculated from the voltage transient responses to current steps injected into the RN neurons. There was no concomitant change in the electrotonic length following the classical conditioning. Furthermore, the fastrising EPSPs were often observed as if they were superposed on the slow-rising EPSPs that were observed in normal animals. These observations suggest that the appearance of fast-rising EPSPs is due to the formation of new corticorubral synapses on the somata or the proximal dendrites of the RN neurons, and not as a result of a reduction in the electrotonic length of the RN neurons. The present study provides further evidence that this type of structural plasticity of synaptic connections underlies establishment of the classically conditioned forelimb flexion.
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  • 7
    ISSN: 1432-1106
    Keywords: Corticothalamic modulation ; Ventroposterolateral thalamus ; Primary and secondary somatosensory cortex (SI and SII) ; Somatosensory thalamus ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of the corticothalamic projections from somatosensory areas I and II (SI and SII) on the transmission of tactile information through the ventroposterolateral (VPL) thalamus was investigated by examining the effects of cooling-induced, reversible inactivation of SI and/or SII on the responsiveness of 32 VPL neurons to controlled tactile stimulation of the distal forelimb in anaesthetized cats. Both the response levels and spontaneous activity were unaffected in 21 (66%) of the VPL neurons as a result of inactivation of SI or SII singly, or both SI and SII simultaneously. In the remaining 11 neurons, 10 displayed a reduction in response level, an effect observed over the whole of the stimulus-response relations for the neurons studied at different stimulus amplitudes, and one neuron displayed an increase in response level in association with cortical inactivation. When responses in VPL neurons were affected by inactivation of one cortical somatosensory area, they were not necessarily affected by inactivation of the other. Of 14 neurons studied for the effects of the separate inactivation of SI alone and of SII alone, 7 were affected, one from both areas, but the remaining 6 were affected by inactivation of only one of these areas. Phaselocking, and therefore the precision of impulse patterning in the responses of VPL neurons to skin vibration, was unchanged by the cortical inactivation irrespective of whether the response level was affected. The results suggest that SI and SII may exert a facilitatory influence on at least a third of VPL neurons and in this way may modulate the gain of transmission of tactile signalling through the thalamus.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 101 (1994), S. 59-72 
    ISSN: 1432-1106
    Keywords: Spinal cord ; Synaptic transmission ; GABAB receptors ; Baclofen agonists and antagonists ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre-and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35 348, 36 742, 46 381, 52 432, 54 626 and 55 845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABAA agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre-and postsynaptic inhibitory effects of 3-aminopropyl-methyl-osphinic acid (CGP 35 024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35 024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABAB receptors. Spinal pre-and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55 845 and 46 381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.
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  • 9
    ISSN: 1432-1106
    Keywords: Omnipause neurons ; Superior colliculus ; Fixation ; Saccade ; Gaze ; Eye-head coordination ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The superior colliculus has long been recognized as an important structure in the generation of saccadic displacements of the visual axis. Neurons with presaccadic activity encoding saccade vectors are topographically organized and form a “motor map.” Recently, neurons with fixation-related activity have been recorded at the collicular rostral pole, at the area centralis representation or fixation area. Another collicular function which deals with the maintenance of fixation behavior by means of active inhibition of orientation commands was then suggested. We tested that hypothesis as it relates to the suppression of gaze saccades (gaze = eye in space = eye in head + head in space) in the head-free cat by increasing the activity of the fixation cells at the rostral pole with electrical microstimulation. Long stimulation trains applied before gaze saccades delayed their initiation. Short stimuli, delivered during the gaze saccades, transiently interrupted both eye and head components. These results provide further support for a role in fixation behavior for collicular fixation neurons. Brainstem omnipause neurons also exhibit fixation-related activity and have been shown to receive a direct excitatory input from the superior colliculus. To determine whether the collicular projection to omnipause neurons arises from the fixation area, the deep layers of the superior colliculus were electrically stimulated either at the rostral pole including the fixation area or in more caudal regions where stimulation evokes orienting responses. Forty-nine neurons were examined in three cats. 61% of the neurons were found to be orthodromically excited by single-pulse stimulation of the rostral pole, whereas only 29% responded to caudal stimulation. In addition, stimuli delivered to the rostral pole activated, on average, omnipause neurons at shorter latencies and with lower currents than those applied in caudal regions. These results suggest that excitatory inputs to omnipause neurons from the superior colliculus are principally provided by the fixation area, via which the superior colliculus could play a role in suppression of gaze shifts.
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  • 10
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Microstimulation ; Gaze saccades ; Tecto-reticulo-spinal neurons ; Fixation ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In our previous paper we demonstrated that electrical microstimulation of the fixation area at the rostral pole of the cat superior colliculus (SC) elicits no gaze movement but, rather, transiently suppresses eye-head gaze saccades. In this paper, we investigated the more caudal region of the SC and its interaction with the fixation area. In the alert head-free cat, supra-threshold stimulation in the anterior portion of the SC but outside the fixation area evoked small saccadic shifts of gaze consisting mainly of an eye movement, the head's contribution being small. Stimulating more posteriorly elicited large gaze saccades consisting of an ocular saccade combined with a rapid head movement. At these latter stimulation sites, craniocentric (goal-directed) eye movements were evoked when the cat's head was restrained. The amplitude of eye-head gaze saccades elicited at a particular stimulation site increased with stimulus duration, current strength, and pulse rate, until a constant or “unit” value was reached. The peak velocity of gaze shifts depended on both pulse rate and current strength. The movement direction was not affected by stimulus parameters. The unit gaze vector evoked, in the head-free condition, by stimulating one collicular site was similar to that coded by efferent neurons recorded at that site, thereby indicating a retinotopically coded gaze error representation on the collicular motor map which is not revealed by stimulating the head-fixed animal. Evoked gaze saccades were found to be influenced by fixation behavior. The amplitude of evoked gaze shifts was reduced if stimulation occurred when the hungry animal fixated a food target. Electrical activation of the collicular fixation area was found to mimic well the effects of natural fixation on evoked gaze shifts. Taken together, our results support the view that the overall distribution and level of collicular activity contributes to the encoding of the metrics of gaze saccades. We suggest that the combined levels of activity at the site being stimulated and at the fixation area influence the amplitude of evoked gaze saccades through competition. When stimulation is at low intensities, fixation-related activity reduces the amplitude of evoked gaze saccades. At high activation levels, the site being stimulated dominates and the gaze vector is specified only by that site's collicular output neurons, from which arises the close correspondence between the unit-evoked gaze saccades and the neurally coded gaze vector at that site.
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  • 11
    ISSN: 1432-1106
    Keywords: Periaqueductal gray ; Tracing Spinal cord ; Axial muscles ; Defense behavior ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The periaqueductal gray (PAG) plays an important role in analgesia as well as in motor activities, such as vocalization, cardiovascular changes, and movements of the neck, back, and hind limbs. Although the anatomical pathways for vocalization and cardiovascular control are rather well understood, this is not the case for the pathways controlling the neck, back, and hind limb movements. This led us to study the direct projections from the PAG to the spinal cord in the cat. In a retrograde tracing study horseradish peroxidase (HRP) was injected into different spinal levels, which resulted in large HRP-labeled neurons in the lateral and ventrolateral PAG and the adjacent mesencephalic tegmentum. Even after an injection in the S2 spinal segment a few of these large neurons were found in the PAG. Wheat germ agglutinin-conjugated HRP injections in the ventrolateral and lateral PAG resulted in anterogradely labeled fibers descending through the ventromedial, ventral, and lateral funiculi. These fibers terminated in lamina VIII and the medial part of lamina VII of the caudal cervical, thoracic, lumbar, and sacral spinal cord. Interneurons in these laminae have been demonstrated to project to axial and proximal muscle motoneurons. The strongest PAG-spinal projections were to the upper cervical cord, where the fibers terminated in the lateral parts of the intermediate zone (laminae V, VII, and the dorsal part of lamina VIII). These laminae contain the premotor interneurons of the neck muscles. This distribution pattern suggests that the PAG-spinal pathway is involved in the control of neck and back movements. Comparing the location of the PAG-spinal neurons with the results of stimulation experiments leads to the supposition that the PAG-spinal neurons play a role in the control of the axial musculature during threat display.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 97 (1994), S. 451-465 
    ISSN: 1432-1106
    Keywords: Binocular ; LGNd ; X and Y cells ; Y-block ; Pressure block ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Binocular non-dominant suppression (NDS) in the dorsal lateral geniculate nucleus (LGNd) of the cat was studied by recording from single neurons in the LGNd of anaesthetized, paralysed cats while stimulating the non-dominant eye with a moving light bar. The maintained discharge rate of LGNd neurons was varied by stimulating the dominant eye in various ways: by varying the size or contrast of a flashed spot, by varying the inner diameter of a flashed annulus of large outer diameter, by varying the velocity of a moving light bar, and by covering the eye. Non-dominant suppression was quantified either as the decrease in the maintained discharge rate (the “dip”), expressed as spikes per second, or as the ratio of the dip to the maintained discharge rate (the “dip ratio”). At low maintained discharge rates the dip, although low in value, frequently approached the maintained rate, i.e. the dip ratio approached unity. As the maintained discharge rate increased the dip value also increased, but more slowly than the maintained discharge rate, i.e. the dip ratio decreased. At maintained discharge rates above about 30 spikes/s, in many neurons the dip appeared to be approaching a constant value. This strong dependence of NDS on the maintained discharge rate of the LGNd neuron suggests that the inhibitory input to the cell arises from a region of the brain that receives an input both from the non-dominant eye and from the LGNd cell. Reasons are given for thinking that this region is the perigeniculate nucleus. Because of the strong dependence of dip and dip ratio on the maintained discharge rate, it was necessary to adopt stringent criteria when comparing NDS in two different sets of neurons or of the same set of neurons in different conditions. We recognized a significant difference in NDS between two classes of neurons or between two states only if: (1) there was no significant difference between the maintained discharge rates, and (2) there was a significant difference for both dip and dip ratio between the two classes or states. Using these criteria we found: (1) no difference between non-lagged X (XNL) and non-lagged Y (YNL) cells, (2) no difference between on-centre and off-centre cells for either XNL or YNL cells, (3) no difference between XNL cells and lagged X (XL) cells. However, there was a significant difference between cells in lamina A and those in lamina A1 for both XNL and YNL cells, dip and dip ratio values being about twice as great in lamina A. In cats in which one optic nerve had been pressure-blocked so as to prevent conduction in the largest axons (Y fibres), loss of conduction in Y fibres crossing the chiasm and projecting to the contralateral LGNd did not affect NDS. Loss of conduction in Y fibres projecting to the ipsilateral LGNd caused a complete loss of NDS in the non-lagged Y cells of lamina A and a substantial decrease in the NDS of the nonlagged X cells of lamina A. The latter cells must, therefore, be partly suppressed by non-Y fibres, presumably X fibres. It also follows that all the NDS of cells in lamina A1 is mediated by non-Y fibres, probably X fibres. Thus, NDS in the cat is partly class-specific and partly not. The discharge of retinal ganglion cells also protects the LGNd cells against NDS. The contribution of Y fibres to this anti-suppressive action was also examined. Contralaterally projecting Y fibres make no contribution. Ipsilaterally projecting Y fibres exert an anti-suppressive action on non-lagged X cells in lamina A1. It follows also that the anti-suppressive action on cells in lamina A mediated by contralaterally projecting fibres is due to non-Y fibres, presumably X fibres. Thus, both the suppressive and the anti-suppressive actions of Y fibres are mediated only by the uncrossed pathway.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 98 (1994), S. 287-297 
    ISSN: 1432-1106
    Keywords: Balance control ; Posture ; Conditioned movement ; Biomechanics ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship between changes in posture and the performance of a forelimb movement required for a transition between two stance positions was analysed in cats. The task consisted of an operantly conditioned, forelimb stepping movement from one support platform to another located more anterior. The reward was given only after a specific vertical force was applied to the second platform. This ensured that the cat performed a clear transition from its initial stance posture to another requiring a different weight distribution. The strategy adopted by an animal during the conditioned movement was studied by analysing the distribution of the vertical forces as a function of time. Specific quantitative functions were used to describe the weight distribution in the anterior-posterior, right-left and diagonal directions as the task was performed. The temporal parameters characterising this behaviour were not significantly different between animals, except for reaction times. In contrast, spatial parameters reflected in the distribution of vertical forces generated during the performance of the task were characteristic for each animal. As a consequence, a variety of strategies were employed. Nevertheless some general features were found, including the persistence of a diagonal support pattern during the phasic part of the movement, and an initial movement to the side of the forepaw performing the movement. The findings support the view that each animal exhibits a specific strategy for performing this well-learned task, and that the strategy is consistently employed over consecutive trials of the movement.
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  • 14
    ISSN: 1432-1106
    Keywords: Carbachol ; Serotonin ; Pontine reticular formation ; Medullary reticulospinal neuron ; Postural atonia ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was aimed at elucidating the pontomedullary and spinal cord mechanisms of postural atonia induced by microinjection of carbachol and restored by microinjections of serotonin or atropine sulfate into the nucleus reticularis pontis oralis (NRPo). Medullary reticulospinal neurons (n=132) antidromically activated by stimulating the L1 spinal cord segment were recorded extracellularly. Seventy-eight of them were orthodromically activated with mono- or disynaptic latencies by stimulating the NRPo area at the site where carbachol injections effectively induced postural atonia. Most of these reticulospinal neurons (71 of 78) were located in the nucleus reticularis gigantocellularis (NRGc). Following carbachol injection into the NRPo, discharge rates of the NRGc reticulospinal neurons (29 of 34) increased, while the activity of soleus muscles decreased bilaterally. Serotonin or atropine injections into the same NRPo area resulted in a decrease in the discharge rates of the reticulospinal neurons with a concomitant increase in the levels of hindlimb muscle tone. Membrane potentials of hindlimb extensor and flexor alpha motoneurons (MNs) were hyperpolarized and depolarized by carbachol and serotonin or atropine injections, respectively. In all pairs of reticulospinal neurons and MNs (n=11), there was a high correlation between the increase in the discharge rates and the degree of membrane hyperpolarization of the MNs. Spike-triggered averaging during carbachol-induced atonia revealed that inhibitory postsynaptic potentials (IPSPs) were evoked in 15 MNs by the discharges of nine reticulospinal neurons. Four of them evoked IPSPs in more than one MN. The mean segmental delay and the mean time to the peak of IPSPs were 1.6 ms and 2.0 ms, respectively. Axonal trajectories of reticulospinal neurons (n=6), which evoked IPSPs in MNs, were investigated in the lumbosacral segments (L1-S1) by antidromic threshold mapping. The stem axons descended through the ventral (n=2) and ventrolateral (n=4) funiculi in the lumbar segments. All axons projected their collaterals to the intermediate region (laminae V, VI) and ventromedial part (laminae VII, VIII) of the gray matter. All these results suggest that the reticulospinal pathway originating from the NRGc is involved in postural atonia induced by pontine microinjection of carbachol, and that the pathway is inactivated during the postural restoration induced by subsequent injections of serotonin or atropine. It is further suggested that the pontine inhibitory effect is mediated via segmental inhibitory interneurons projecting to MNs.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 99 (1994), S. 399-410 
    ISSN: 1432-1106
    Keywords: Amblyopia ; Visual cortex ; Monocular deprivation ; Reverse suturing ; Area 17 ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Receptive field properties of extracellularly recorded units in the visual cortex (area 17) of cats made bilaterally amblyopic by a variety of rearing conditions were measured and compared with the properties of units in normal cats. Properties studied included sensitivity to vernier offset, response facilitation to increasing bar length, receptive field size, responsiveness to moving and flashed stimuli, orientation tuning, the relation between mean firing rate and its variance, the amount of overlap of regions of on and off responsiveness in simple and complex cells, and, for flashed stimuli, latency to response onset, time to peak response, and response decay time constant. Behavioural testing of the amblyopic animals showed that spatial resolution was 2–4 times lower and vernier acuity thresholds 10–20 times greater than normal. Despite this, several neuronal response properties did not differ significantly from those in normal animals. These included peak responsiveness to moving stimuli, widths of orientation tuning curves, response variability, and latency to initial response for flashed stimuli. Other properties showed small but significant changes. Sensitivity to vernier offset (impulses per degree of offset) was reduced to nearly half its normal level; receptive field sizes increased by about 24% and an incomplete segregation of regions of on and off responsiveness was found in some cells, which made them hard to classify as simple or complex. Responses to flashed stimuli were smaller and more persistent. Their statistical significance notwithstanding, it seems unlikely that these relatively small response abnormalities in area 17 can fully account for the observed behavioural deficits.
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  • 16
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    Experimental brain research 98 (1994), S. 213-228 
    ISSN: 1432-1106
    Keywords: Fictive locomotion ; Proprioception ; Spinal cord ; Interneurones ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been previously shown that phasic stimulation of group I afferents from ankle and knee extensor muscles may entrain and/or reset the intrinsic locomotor rhythm; these afferents are thus acting on motoneurones through the spinal rhythm generators. It was also concluded that the major part of these effects originates from Golgi tendon organ Ib afferents. Transmission in this pathway to lumbar motoneurones has now been investigated during fictive locomotion in spinal cats injected with nialamide and l-DOPA, and in decerebrate cats with stimulation of the mesencephalic locomotor region. In spinal cats injected with nialamide and l-DOPA, it was possible to evoke long-latency, long-lasting reflexes upon stimulation of high threshold afferents before spontaneous fictive locomotion commenced. During that period, stimulation of ankle and knee extensor group I afferents evoked oligosynaptic excitation of extensor motoneurones, rather than the “classical” Ib inhibition. Furthermore, a premotoneuronal convergence (spatial facilitation) between this group I excitation and the crossed extensor reflex was established. During fictive locomotion, in both preparations, the transmission in these group I pathways was phasically modulated within the step cycle. During the flexor phase, the group I input cut the depolarised (active) phase in flexor motoneurones and evoked EPSPs in extensor motoneurones; during the extensor phase, the group I input evoked smaller EPSPs in extensor motoneurones and had virtually no effect on flexor motoneurones. The above results suggest that the group I input from extensor muscles is transmitted through the spinal rhythm generator and more particularly, through the extensor “half-centre”. The locomotor-related group I excitation had a central latency of 3.5–4.0 ms. The excitation from ankle extensors to ankle extensors remained after a spinal transection at the caudal part of L6 segment; the interneurones must therefore be located in the L7 and S1 spinal segments. Candidate interneurones for mediating these actions were recorded extracellularly in lamina VII of the 7th lumbar segment. Responses to different peripheral nerve stimulation (high threshold afferents and group I afferents bilaterally) were in concordance with the convergence studies in motoneurones. The interneurones were rhythmically active in the appropriate phases of the fictive locomotor cycle, as predicted by their response patterns. The synaptic input to, and the projection of these candidate interneurones must be fully identified before their possible role as components of the spinal locomotor network can be evaluated.
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  • 17
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    Experimental brain research 98 (1994), S. 39-43 
    ISSN: 1432-1106
    Keywords: Optic nerve regeneration ; Myelin sheath Electron microscopy ; g value ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Retinal ganglion cells of adult cats have the potential to regenerate their axons into autografted peripheral nerve. Two months after transplantation of the sciatic nerve to the axotomized optic stump, regenerated axons were labeled anterogradely with biocytin, and myelin formation by Schwann cells was examined electron microscopically. Both myelinated and unmyelinated fibers were labeled with biocytin. Among 511 axons labeled in three grafts, 96 fibers (18.8%) were myelinated and 415 (81.2%) were unmyelinated. Mean diameter with SD of myelinated fibers was 1.28 ± 0.39 μm (range 0.71–2.47) and that of unmyelinated fibers was 0.76± 0.38 μm (range 0.18–2.46). The ratio of inner to outer diameters of the myelin sheath (g value) was 0.82, which is close to the value (0.8) for the optic fibers of intact adult cats.
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  • 18
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    Experimental brain research 98 (1994), S. 379-390 
    ISSN: 1432-1106
    Keywords: Eye movements ; Vestibulo-ocular reflex ; Motor learning and plasticity ; Flocculus ; Climbing fibers ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Motor learning can be demonstrated in the vestibulo-ocular reflex (VOR) by changing its gain (eye velocity/head velocity) with goggles and optokinetic (OK) drums. It is known that the flocculus is essential for this plasticity but there is controversy about whether the modifiable synapses mainly responsible are in the flocculus. To investigate this further we utilized the known reciprocal relationship between complex spikes and simple spikes in Purkinje cell discharges. By stimulating climbing fibers from the olive to the flocculus at 7 Hz, the simple spike rate of almost all recorded floccular cells could be driven to zero. This was termed floccular shutdown and is felt to effect a functional, reversible flocculectomy. Sixty single units in the flocculi of four cats were recorded. Stimulation of the climbing fibers at 7 Hz caused the discharge rate to decrease to zero in 95% of these cells. The gain of the horizontal VOR in three cats was driven repeatedly to twice or half its normal value by rotation within a moving OK drum and also by wearing magnifying or fixed-field goggles; this process required 3 days. If, on the 4th day, the cat was exposed to an OK drum rotating in the opposite direction, the gain was driven back to normal in 30 min. If, however, the climbing fibers were stimulated at 7 Hz during these 30 min, the gain did not return — learning was blocked. This verified that loss of floccular activity by this method abolishes VOR gain plasticity. Moreover, when 7 Hz stimulation first began, after 3 days of adaptation, the adapted gain remained at its adapted value, either half or twice normal, even in the face of floccular shutdown. This result appears incompatible with the hypothesis that the modifiable synapses are in the flocculus.
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  • 19
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    Experimental brain research 99 (1994), S. 170-174 
    ISSN: 1432-1106
    Keywords: Vision ; Visual cortex ; Receptive fields ; Complex neurons ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Excitatory receptive field (ERF) response profiles and length summation functions were derived from complex neurones in cat striate cortex. Measured length summation was compared with summation predicted from integration over ERF profiles. In a minority of neurones, measured and predicted summation were well matched. In the majority, whether end-stopped or not, responsiveness in length summation tests was appreciably greater than predicted for short stimuli, compared with ERF profiles. The mismatch was least in standard and greatest in special complex neurones; in the latter group, response levels to long stimuli fell well below predicted levels. In end-stopped neurones the decremental portion of length summation functions was not predicted by ERF profiles. These results implicate the involvement of non-linear mechanisms, whereby concomitant stimulation of central regions of the receptive field (RF) potentiate the efficacy of loci towards either end of the RF.
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  • 20
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    Experimental brain research 98 (1994), S. 172-177 
    ISSN: 1432-1106
    Keywords: Visual cortex ; Directionality Width summation ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Width summation of complex neurones in cat striate cortex was assessed for moving sine-wave gratings. Summation was restricted in special complex neurones, approximately matched receptive field width in intermediate complex neurones and exceeded it in most standard complex neurones. Responses to preferred and opposite directions of motion were compared: 12 of 20 complex neurones showed similar directional bias for moving sinewave gratings and for single moving bars of either contrast polarity; 8 of 20 were similarly or more weakly direction-selective for bars than for grating patches, dependent on patch width. In two of these, this was despite the fact that the directional bias for gratings was invariant with patch width. In the remaining six, differences could be accounted for by progressive increase or decrease in directional bias for gratings, as grating patch width was systematically increased. In conclusion, directional bias of a substantial proportion of complex cells is determined by stimulus configuration.
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  • 21
    ISSN: 1432-1106
    Keywords: Temporal filtering ; Lateral geniculate nucleus ; Signal transmission ; Signal transmission ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dependency of intrageniculate signal transfer on stimulus temporal frequency was investigated by comparing responses of individual X-relay cells with their direct retinal inputs in anesthetized and paralyzed cats. Temporal frequency response functions of lateral geniculate nucleus (LGN) X-cells were more narrowly tuned than those of their retinal inputs. The efficiency of signal transfer was consistently highest at or around the geniculate cells' optimal temporal frequency, and the degree of signal transfer, which was more closely related to the LGN cells' firing rate than to the firing rate of their retinal input, decreased for both lower and higher temporal frequencies. The high temporal frequency cut-offs were significantly lower in geniculate cell responses than those of their direct retinal inputs. This reduction in temporal resolution was exaggerated for relatively low stimulus spatial frequencies. The present results provide clear evidence for the notion that LGN cells function as nonlinear temporal filters and that this stimulus-dependent signal transmission appears to be regulated by complex local mechanisms.
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  • 22
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    Experimental brain research 79 (1994), S. 369-375 
    ISSN: 1432-1106
    Keywords: Calcium entry blocker ; Electrical potential ; Interstitial ion activity ; Spinal cord injury ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interstitial and tissue cations and electrical potential were studied in an experimental model of spinal cord contusion injury in anaesthetised cats. Measurements of interstitial ion activity in the grey matter at the injury site (with ion-selective electrodes), showed a decrease of sodium and calcium, an increase of potassium, a small acidification and a negative shift in the electrical potential 5 min after injury. The interstitial ionic changes were completely reversible within 90 min following injury. Measurements of the ion content in a tissue sample from the injury site (flame photometry) showed an increase of sodium and calcium and a decrease of potassium 5 min after injury. The magnitude of the post-injury sodium change was much larger than the potassium change, both for interstitial and tissue measurements. Treatment of the animals with the calcium entry blocker flunarizine before the injury did not influence the magnitude of post-injury interstitial calcium decrease but significantly increased the rate of subsequent recovery. Pre-injury flunarizine treatment also significantly increased the recovery rate of the electrical potential. The experiments suggest the occurrence of a net ionic shift towards the intracellular space, which may contribute to oedema formation in the very early post-injury period. The post-injury decrease of interstitial calcium activity is probably not mediated by flunarizine-sensitive calcium entry mechanisms; such mechanisms may, however, be involved in the subsequent recovery period for interstitial calcium activity. Calcium ions may be involved in the recovery process of the negative electrical potential after injury.
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  • 23
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    Experimental brain research 98 (1994), S. 31-38 
    ISSN: 1432-1106
    Keywords: Striate cortex ; Spatial frequency tuning ; Orientation sensitivity ; Intracortical inhibition ; Bicuculline methiodide ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Responses of simple and complex cells in cat striate cortex were studied with moving sine-wave gratings before and during application of the GABAA receptor antagonist bicuculline methiodide. Both simple and complex cells exhibited a broadening of their spatial frequency tuning functions under bicuculline. This was especially evident at spatial frequencies lower than the ones the cell was responding to before the drug administration. The effects cannot be explained by response saturation and could be reversed by cessation of the iontophoresis. The results indicate that the band-pass response characteristics of the spatial frequency response functions of striate cells derive largely from intracortical inhibition. The findings have implications also for the orientation selectivity of cortical cells. Since many geniculate cells are tuned for stimulus orientation at higher spatial frequencies, suppression of the low-spatial-frequency component would remove some of the orientation non-specific response in striate cortical cells and contribute to their orientation selectivity.
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  • 24
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    Experimental brain research 98 (1994), S. 53-64 
    ISSN: 1432-1106
    Keywords: Single units ; Inferior colliculus ; Organization ; Vocal stimuli ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to gain information from anesthetized cats about the differential coding properties of neurons in the three major subdivisions of the inferior colliculus: the central (CNIC) and external (EN) nuclei and dorsal cortex (DC). Stimuli were presented in the free field from a speaker facing the contralateral pinna. For each unit, the characteristic frequency (CF, where threshold was lowest) was determined, and impulse rates to CF tone bursts, noise bursts and four feline vocal stimuli were measured as a function of increasing sound pressure level (rate/level functions). Peristimulus-time histograms were computed for responses to all stimuli. Sustained firing patterns to CF stimuli were observed for 81% of units in CNIC, for 50% of units in EN and 27% of units in DC. Sustained discharges were evoked by noise in 78–100% of units in all regions, and by at least one vocal stimulus in 86% of units in CNIC, 82% in EN and 55% in DC. In the CNIC, non-monotonic rate/level functions to CF stimuli were more common (41%) than either monotonie or plateau functions, whereas the reverse was the case with noise and vocal stimuli. Non-monotonic functions were uncommon to any stimulus in EN and DC (21–24%). Vocal stimuli were more effective in terms of higher firing rates than noise or CF stimuli in 27% of units in CNIC, 82% in EN and 72% in DC. There were no units that responded exclusively to one vocal stimulus, but a high proportion of units in EN responded strongly to broad band stimuli, and some of these showed clear preferences for one vocal stimulus over others.
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  • 25
    ISSN: 1432-1106
    Keywords: Inspiratory neurons ; Hypoglossal motoneuron ; Phrenic motoneuron ; Dual-projection neuron ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Localization and projection to the phrenic (PH) nucleus were studied in a sample of premotor neurons that directly projected to hypoglossal motoneurons (XII Mns) and showed respiratory-related patterns of activity. The experiments were carried out in cats, under pentobarbital anesthesia. In the first part of the study, the retrograde double-labeling technique was used to reveal the existence of neurons projecting to both the XII and the PH nuclei. Injection of a fluorescent dye (fast blue, FB) into the XII nucleus and another (nuclear yellow, NY) into the PH nucleus retrogradely labeled, with either FB or NY, medullary reticular neurons mainly in the regions ventrolateral to the nucleus of the tractus solitarius (vl-NTS), ventrolateral to the hypoglossal nucleus (vl-XII), and dorsomedial to the nucleus ambiguus (dm-AMB) bilaterally. In addition, some neurons in these regions were labeled with both FB and NY. In the second part of the study, unitary activity was recorded extracellularly from medullary respiratory neurons. In the regions vl-NTS, vl-XII, and dm-AMB, inspiratory neurons were found which antidromically responded to stimulation of the XII nucleus. Some of them also responded antidromically to stimulation of the PH nucleus. Averaging of rectified and integrated XII and PH nerve discharges by spontaneous spikes of single inspiratory neurons in the vl-NTS and dm-AMB regions revealed a facilitation in either XII nerve discharge or both XII and PH nerve discharges after a short latency of monosynaptic range. It is concluded that in the vl-NTS and dm-AMB regions there are inspiratory neurons that are excitatory premotor neurons projecting to XII Mns showing the respiratory-related activity. Some of them have excitatory synaptic connections to XII and PH Mns via bifurcating axons.
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  • 26
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    Experimental brain research 102 (1994), S. 175-180 
    ISSN: 1432-1106
    Keywords: Striate cortex ; Simple cells ; Single spot stimuli ; Axis preference ; Influence of velocity ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Directional tuning for motion of a long bar and a spot was compared quantitatively over a wide range of velocities in 23 simple cells of cat striate cortex whose “on” and “off” receptive field subregions had been mapped with optimally oriented, stationary flash-presented bars. Tuning curves were derived using stimuli whose polarity of contrast was appropriate for the dominant receptive field subregion of each cell (i.e. light stimuli for on-subregions and dark stimuli for off-subregions); stimulus sweep was centred accurately on the centre of that subregion. Bar stimuli were of optimal width, and spot diameter was equal to the width of the bars. In all simple cells, preferred axis of motion for a long bar was invariant with velocity, being orthogonal to preferred orientation, as assessed with a stationary flash-presented bar. In 20 of 23 simple cells, preferred axis for spot motion was approximately orthogonal to that for bar motion (i.e., parallel to preferred orientation) at all velocities tested, including those just above threshold for spot stimuli. However, tuning for the spot became sharper as velocity was increased, due to an increase in response to the spot moving along the preferred axis and a decrease in response to spot motion along other axes, including the preferred axis for the bar. Both preferred and upper cut-off velocity were consistently higher for spot than for bar motion. The remaining 3 simple cells showed no response to spot motion at any velocity, and their preferred axis of motion for the shortest bar which evoked a consistent response was the same as that for a long bar. We conclude that simple cells respond to motion of a spot per se and not just to its oriented components, and that in most simple cells preferred axis for spot motion is genuinely approximately orthogonal to that for motion of a long bar. A spatio-temporal filter model incorporating intracortical feedforward facilitation along the long axis of the receptive field can account for the observed differences in axis preference and velocity sensitivity for spot and bar motion.
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  • 27
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    Experimental brain research 102 (1994), S. 319-326 
    ISSN: 1432-1106
    Keywords: Visual cortex ; Simple cells ; Mach bands ; Receptive fields ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mach bands are a visual illusion evoked by a luminance ramp dividing two luminance plateaux (blurred edges), but not by sharp edges. Recently, two physiology-based models have tried to cope with the psychophysical data concerning this phenomenon. The basic components of both models are neurons with even- or odd-symmetric receptive fields (RFs). Both models predict that odd-symmetric cells respond better to sharp edges, while even-symmetric cells respond better to blurred ones. We have measured the responses of 34 primary visual cortex simple cells of the cat to blurred edges of various degrees. Twenty-one cells had RFs of even symmetry, responding best to blurred edges than to sharp ones. The rest were odd-symmetric cells, of which 12 responded best to sharp edges, and only one exceptional cell responded best to a 0.85°-wide edge. Thus, the different cell types responded as predicted by the two different Mach band models. Simple cells may thus serve as the physiological basis of the psychophysical phenomenon of Mach bands. Furthermore, our evidence suggests the existence of inhibition between odd-and even-symmetric cells, as predicted by one of the models.
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  • 28
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    Experimental brain research 101 (1994), S. 452-464 
    ISSN: 1432-1106
    Keywords: Somatosensory thalamus ; Knee joint ; Nociception ; Bradykinin ; Capsaicin ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to gain insight into the representation of articular pain of the knee at the supraspinal level, recordings were made from lateral thalamic neurons receiving input from afferent fibres of the knee joint in chloralose-anaesthetized cats. Dorsoventral penetrations were made through the ventral posterior lateral nucleus (VPL) using high intensity electrical stimulation of the medial articular nerve (MAN), which contains a high proportion (80%) of Aδ and C afferent fibres. All recording sites were verified histologically. Close retrograde injections (300 μl over 6 s) into geniculate artery of KCl (2 × isotonic), bradykinin (BK, 2.6 or 26 μg) and capsaicin (200 μM) were used to test the response properties of thalamic neurons. Of the 50 MAN-positive units tested, 20 showed a response to intra-arterial KCl; of these 20, 12 had a response to BK; 8 of these 12 units were additionally tested with capsaicin and all responded. KCl and capsaicin injections had similar mean response latencies (4.5 and 6.8 s), whereas BK had a longer mean latency (18.6 s). The mean peak response was greatest for capsaicin (168 impulses/s), then KCl (87.5 imp/s) and least with BK (36.4 imp/s). The mean response duration was longest with capsaicin (118 s), followed by BK (67.5 s) and least with KCl (27.9 s). Most of these were convergent wide dynamic range (WDR) neurons with a deep receptive field in the knee joint and hindlimb muscle and/or cutaneous distal hind limb digit, located to the dorsal or ventral periphery of the lateral division of the VPL, the VPLl. In addition, 8 neurons showed inhibitory responses to KCl and/or BK injections. The background activity of the VPLl neurons activated by saphenous nerve stimulation was inhibited by the nociceptive articular stimulus with a magnitude and time course which mirrored the excitatory responses in the periphery of VPLl. These results support the concept that the lateral thalamus plays an important role in mediating discriminative aspects of joint pain.
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  • 29
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    Experimental brain research 98 (1994), S. 101-109 
    ISSN: 1432-1106
    Keywords: Tendon jerk ; Fusimotor ; Reflex Muscle spindle ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This is a study of the tendon jerk reflex elicited by a brief stretch applied to the triceps surae muscle group in the chloralose-anaesthetised cat. The size of the recorded reflex depended on stretch parameters (optimum at 300 μm amplitude at a rate of 100 mm/s) and on how the muscle had been conditioned. A reflex elicited after a conditioning contraction at the test length was often twice as large as after a contraction carried out at a length longer than the test length. This difference was attributed to the amount of slack introduced in the intrafusal fibres of muscle spindles by conditioning. The question was posed, did ongoing fusimotor activity exert any influence on the size of the tendon jerk? Depolarization indices (DPI) were calculated from responses of muscle spindles to stretch and correlated with the level of reflex tension. Values of DPI obtained from afferent responses with and without repetitive stimulation of identified fusimotor fibres suggested that with the stretch parameters used here the main influence of fusimotor activity was that it removed any pre-existing slack in muscle spindles and thereby increased reflex tension. In the absence of intrafusal slack, stimulation of static and dynamic fusimotor fibres had little additional influence on the size of the reflex. It is concluded that much of the variability typically seen with tendon jerks is due to muscle history effects. Since in muscles which have not been deliberately conditioned there is commonly some slack present in spindles, activity in fusimotor fibres is likely to reduce slack and therefore increase reflex size.
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  • 30
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    Keywords: Optokinetic nystagmus and afternystagmus ; Vestibuloocular reflex ; Adaptation and habituation ; Vestibulocerebellum ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bilateral surgical lesions of the flocculus or the nodulo-uvular lobes were performed in the cat. Effects of these lesions on optokinetic and optokinetic afternystagmus (OKAN), vestibulo-ocular reflex (VOR), visual suppression, and adaptation and habituation of VOR were studied using an identical experimental protocol. After flocculectomy, all these functions were impaired, except for habituation. Long-term postoperative recordings only revealed a recovery of the suppression of VOR, suggesting a limited contribution of the flocculus to this function. After nodulo-uvulectomy, only habituation and OKAN were modified. When the lesion was restricted to part of the uvula, OKAN duration was decreased. For other lesions involving the uvula together with the nodulus and/or the lobules VII-VIII, OKAN duration was increased. Habituation was lost after destruction of the nodulo-uvular lobes. When this latter structure was damaged, the retention component of habituation was selectively impaired, sparing the acquisition. Additional lesions outside the vestibulocerebellum appeared necessary to suppress the two components. Comparison of results obtained after flocculectomy and after nodulouvulectomy confirms and extends to nonprimate species the concept of a “differential control” of adaptation and habituation by distinct vestibulocerebellar structures.
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  • 31
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    Experimental brain research 98 (1994), S. 546-550 
    ISSN: 1432-1106
    Keywords: Neck muscles ; Cervical vertebrae ; Voluntary head tracking ; Control strategies ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The focus of these experiments was to determine the relationships between head movement, neck muscle activation patterns, and the positions and movements of the cervical vertebrae. One standing cat and one prone cat were trained to produce voluntary sinusoidal movements of the head in the sagittal plane. Video-opaque markers were placed on the cervical vertebrae, and intramuscular patch electrodes implanted in four muscles of the head and neck. Cinefluoroscopic images of cervical vertebral motion and electromyographic responses were simultaneously recorded. Analysis of the spinal movement revealed that the two cats used different strategies to keep their heads aligned with the tracker. In the standing cat, vertebral motion described a more circular arc, compared to a forward diagonal in the prone cat. Intervertebral motion was limited, but more acute angles appeared between the vertebrae of the prone lying than of the standing animal. Data revealed that the central nervous system could control several axes of motion to keep the cervical spine matched to the moving stimulus. Phase relations between the sinusoidal motion of the vertebral column, peak activation of the neck muscles, and that of the stimulus were examined, and several different control strategies were observed both between and within animals. The results suggest that the central nervous system engages in multiple strategies of musculo-skeletal coordination to achieve a single movement outcome.
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  • 32
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    Experimental brain research 102 (1994), S. 198-209 
    ISSN: 1432-1106
    Keywords: Primary spindle afferents ; Secondary spindle afferents ; Classification ; Discharge pattern regularity ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discharge frequency of primary (Ia) and secondary (II) muscle spindle afferents from the tibial anterior muscle of the cat were recorded under a rampand-hold stretch of the host muscle. The rate of ramp stretch and the prestretch of the muscle were varied systematically. The degree of stretch was kept constant. For a discharge pattern recorded at a ramp rate of 10 mm/s, the peak dynamic discharge, the maximum static value and the final static value were determined. These three discharge rate values were plotted against the maximum static value. In the resulting charts the II afferents presented themselves as a homogeneous group of spindle afferents, whereas the Ia fibers separated into three subgroups. The existence of three subpopulations of Ia fibers was verified by the method of Hald. Furthermore, it is shown that each subpopulation generated its discharge patterns in its own regularly systematic manner. It was concluded that, as one of the three Ia subpopulations exhibits much the same dynamic and static stretch properties as the II fibers, the encoder of this subpopulation must receive its receptor current from the sensory terminals of passive intrafusal chain fibers. The encoder of a second Ia subpopulation indicates its action potentials using the receptor current stemming from the bag1 sensory terminals, these Ia fibers eliciting a slow adaptation component of a high magnitude which is assumed to be the consequence of a high level of “creep” in the passive intrafusal bag1 fiber. The third Ia subpopulation initiates its action potential sequences by means of the receptor current stemming from the passive bag2 fiber, producing behavior patterns that lie between those of the other two Ia subpopulations.
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  • 33
    ISSN: 1432-1106
    Keywords: Globus pallidus ; Entopeduncular nucleus GABA ; Muscimol ; Bicuculline ; Reaction time Intracerebral microinjection ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible role of GABAergic mechanisms in the control of the basal ganglia output structures, the globus pallidus (GP) and the entopeduncular nucleus (EP), was studied in cats performing a conditioned flexion movement triggered by an auditory stimulus. The effects of discrete unilateral microinjections of low doses of the GABAA receptor agonist (muscimol 5–100 ng/ 0.5 μl) and antagonist (bicuculline methiodide 25–150 ng/0.5 μl) in the GP and the EP were tested on the motor performance of eight animals trained to release a lever in a simple reaction time (RT) schedule after an auditory stimulus. Control injections in neighboring structures did not induce any effect except with five- to tenfold higher doses in the closest injection sites. The dose of 20 ng muscimol injected into the ventral and medial part of the GP produced an arrest of the performance after a few unsuccessful trials (over the RT reinforcement limit of 500 ms), while muscimol injected in sites located in the lateral GP resulted in a dose-dependent lengthening in RTs, with a concomitant increase in the force change latency. In most of the subjects, the force exerted on the lever was higher after muscimol than after vehicle injection. Force change velocity was then significantly increased. In contrast, muscimol injected in the ventral and rostral region of the EP produced a decrease in RTs or a complete cessation of responding after a high number of anticipatory responses (release of the lever before the trigger stimulus). No significant changes in the force change latency could be observed while there was a non-significant tendency for the force levels to be lowered. Bicuculline injections in the EP were found to increase RTs with a concomitant increase in force change latency and a slowness of velocity, while no significant effect was observed following injections in the GP. These results suggest that a balance between GABAergic activity in the two output nuclei of the basal ganglia, the GP and the EP, is crucial for the correct initiation and execution of the conditioned motor task.
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  • 34
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    Experimental brain research 102 (1994), S. 210-226 
    ISSN: 1432-1106
    Keywords: Primary auditory cortex ; Frequency representation ; Intensity representation ; Single neuron ; Cortical topography ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tonotopicity of the cat's primary auditory cortex (AI) is thought to provide the framework for frequency-specific processing in that field. This study was designed to assess this postulate by examining the spatial distribution of neurons within AI that are activated by a single tonal frequency delivered to the contralateral ear. Distributions obtained at each of several stimulus levels were then compared to assess the influence of stimulus amplitude on the spatial representation of a given stimulus frequency in AI. Data were obtained from 308 single units in AI of four adult, barbiturate-anesthetized cats, using extracellular recording methods. Stimuli were 40-ms tone pulses presented through calibrated, sealed stimulating systems. In each animal, the CF (stimulus frequency to which the unit is most sensitive), threshold at CF, response/level function at CF, and binaural interactions were determined for isolated neurons (usually one per track) in 60–90 electrode tracks. For each unit, regardless of its CF, responses to 40 repetitions of contralateral tones of a single frequency, presented at each of four or five sound pressure levels (SPLs) in the range from 10 to 80 dB were obtained. Different test frequencies were used in each of four cats (1.6, 8.0, 11.0, and 16.0 kHz). For tones of each SPL, we generated maps of the response rates across the cortical surface. These maps were then superimposed on the more traditional maps of threshold CF. All units whose CF was equal to the test frequency could be driven at some SPL, given an appropriate monaural or binaural configuration of the stimulus. There was a clear spatial segregation of neurons according to the shapes of their CF tone response/level functions. Patches of cortex, often occupying more than 2 mm2, seemed to contain only monotonic or only nonmonotonic units. In three cortices, a patch of nonmonotonic cells was bounded ventrally by a patch of monotonie cells, and in one of these cases, a second patch of monotonic cells was found dorsal to the nonmonotonic patch. Contralateral tones of any given SPL evoked excitatory responses in discontinuous cortical territories. At low SPLs (10, 20 dB), small foci of activity occurred along the isofrequency line representing the test frequency. Many of these cells had nonmonotonic response/level functions. At mid- and high SPLs, the CFs of neurons activated by a pure tone varied across 3 octaves. At the highest SPL used (80 dB), most of the neurons with nonmonotonic response/level functions were inactive, or responded poorly; the active neurons were widely spread across the cortex, and the distribution of activity had a pattern bearing little relationship to the threshold CF contour map. These data indicate that only isolated patches of units within the relevant isofrequency contour are activated by a given suprathreshold contralateral tone. At suprathreshold stimulus levels, the region of cortex containing active patches extends widely beyond the threshold isofrequency contour region corresponding to the test stimulus frequency. The spatial representation of a stimulus delivered to the contralateral ear appears, therefore, to be highly level dependent and discontinuous. These observations suggest that in the cat's AI, tonotopicity and isofrequency contours are abstractions which bear little resemblance to the spatial representation of tonal signals.
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  • 35
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    Experimental brain research 100 (1994), S. 58-66 
    ISSN: 1432-1106
    Keywords: Muscle spindle ; Fusimotor Succinyl choline ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report describes the effects of succinylcholine (SCh) on the secondary endings of cat soleus muscle spindles and attempts to explain them in terms of the action of the drug on intrafusal fibres. All but 2 of 41 secondary endings studied in detail showed a significant response to a single intravenous injection of 200 μg kg-1 SCh. This consisted of a rise in the resting rate or development of a resting discharge if the spindle had previously been silent and an increase in the response to stretch. The increases in the responses to stretch were weaker than those observed for primary endings of spindles, but were much larger than those of tendon organs, which showed very little effect with this concentration of drug. The response to SCh showed two features consistent with its action being mediated via an intrafusal muscle fibre contraction rather than a direct depolarising action on the afferent nerve ending. In the presence of SCh, secondary endings were able to maintain a discharge during muscle shortening at rates, on average, more than 5 times greater than under control conditions. Secondly, the increase in spindle discharge produced by SCh showed a length dependence similar to that for fusimotor stimulation. Further support for the action of SCh being principally via an intrafusal fibre contraction was provided by the observation that its effects were abolished by the neuromuscular blocker gallamine triethiodide. The time course of recovery of SCh responses, following their blockade by gallamine, was much slower than recovery of extrafusal tension and closely paralleled that for the recovery of fusimotor responses. In three separate experiments on the medial gastrocnemius muscle the possibility that SCh may exert an excitatory action on spindle sensory endings through the liberation of potassium ions from the muscle was tested by tetanic stimulation of the muscle. This had no detectable excitatory effect. Several observations were made on the effect of SCh on responses of cutaneous receptors. SCh did not change levels of spontaneous activity or responses to mechanical stimulation of either slowly or rapidly adapting mechanoreceptors. It was argued for both tendon organs and cutaneous receptors that if SCh had a direct action on the nerve ending at the concentrations used here, some responses of these receptors to the drug might have been expected. All of the above supports the view that secondary endings of spindles are able to respond to SCh by the development of an intrafusal fibre contracture. The question of the intrafusal fibre types involved is discussed.
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  • 36
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    Experimental brain research 100 (1994), S. 149-154 
    ISSN: 1432-1106
    Keywords: Long-term potentiation ; GABAA receptor ; NMDA receptor ; Low-threshold calcium channel ; Motor cortex ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term potentiation of synaptic transmission (LTP), as documented by the enhancement of evoked field potentials in layer III following stimulation of the underlying white matter, has been studied in slices of motor cortex from adult cats. With a 1 M NaCl-filled recording electrode, LTP was induced only in one out of eight slices. When the recording electrode in addition contained 5 mM bicuculline metiodide, LTP was obtained with a much higher rate of success (15/19), suggesting that reduction of GABAA receptor-mediated inhibition facilitated the induction of LTP in the motor cortex. Bath application of dl-2-amino-5-phosphonovaleric acid (APV, 100 μM) or Ni2+ (100 μM) significantly reduced the success rate for LTP occurrence (6/16 and 5/16, respectively); but when LTP was induced, it did not show significant change in magnitude and time course. In slices perfused with APV (100 μM) plus Ni2+ (100 μM), LTP induction was completely blocked (0/12). These results suggest that two different mechanisms may subserve LTP induction in the cat motor cortex: one is mediated by N-methyl-d-aspartate receptors and can be blocked by APV; the other may be mediated by low-threshold calcium channels and can be blocked by Ni2+.
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  • 37
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    Experimental brain research 100 (1994), S. 160-164 
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Tecto-spinal neurons ; Spinal cord ; WGA-HRP ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Injections of WGA-HRP were made within the C1 segment of spinal cord in cats with a midsagittal section of the midbrain. A small number of labelled cells were found in the latero-caudal part of the deeper layers of the superior colliclus (SC) ipsilateral to the injection sites. Because of the complete section of the dorsal tegmental decussation, these results definitively demonstrate the existence of an ipsilateral tecto-spinal pathway projecting to upper cervical segments in the cat. Ipsilaterally projecting tecto-reticulo-spinal neurons represent about 5% of the total population of tectospinal neurons. They were exclusively located in the deeper collicular layers and most of them were found in the latero-caudal part of the SC. Comparison with our previous studies suggests that more ipsilateral tectospinal projections that found after the section of the dorsal tegmental decussation probably exist. They may arise from tecto-reticulo-spinal neurons recrossing the midline in the brainstem or in the rostral part of C1. By analogy with the cortico-spinal tract, we suggest that the existence of an ipsilateral tecto-spinal pathway can be regarded as evidence for a substantial development of the cat tecto-spinal system as compared with other mammals.
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  • 38
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    Experimental brain research 100 (1994), S. 187-199 
    ISSN: 1432-1106
    Keywords: Forel's field H Orienting head movements ; Vertical Single unit recording ; Head-free ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Single unit activities were recorded in Forel's field H (FFH) at the mesodiencephalic junction during orienting head movements in two alert cats under headfree conditions. Recordings were made of 63 neurons of which 20 showed phasic firing that preceded the onset of head movements by 20–100 ms and was temporally related to the dynamic phase of the orienting head movement. Nineteen of these neurons showed a preference for upward movements, while the remaining neuron preferred downward movements. Activities during orienting movements in eight different directions (each separated by 45°) were systematically analyzed for 12 of the 19 upward-preferring neurons. The activities were broadly tuned; in most of the neurons, maximum activity was observed for direct upward movements (+90°), but significant activity was also observed for ipsilateral and contralateral oblique upward movements (+45° and +135°). In these cases, the increase in activity preceded the onset of the movement. Some increase in activity was also observed for ipsilateral and contralateral horizontal, oblique downward and downward movements. However, the increase in activity in the latter cases occurred simultaneously with or lagged behind the onset of the movement and was often preceded by a decrease in activity. The same pattern of directional tuning was observed in the EMG of the biventer cervicis muscle, a target of FFH neurons. The preferred directions of the 12 upward-preferring neurons were estimated by calculating the vector sum of the activity and were distributed between +68° and +108°. The same amount of activity was observed for ipsilateral and contralateral oblique upward movements, suggesting that FFH neurons on both sides of the brainstem are equally activated even during oblique orienting. Input from the ipsilateral superior colliculus was investigated in 18 neurons, all of which were orthodromically activated with a latency of 0.8–1.8 ms, suggestive of a mono- or disynaptic excitatory connection. Seven neurons were identified as descending projection neurons by antidromic activation from the ipsilateral medullary reticular formation. Repetitive microstimulation of unilateral FFH induced oblique upward head movements and an accompanying torsional component, while simultaneous bilateral stimulation at comparable stimulus strength induced purely upward head movements. These results strongly suggest that the vertical component of orienting head movements is encoded by equal bilateral activation of the FFH.
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  • 39
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    Experimental brain research 100 (1994), S. 215-226 
    ISSN: 1432-1106
    Keywords: Thalamic reticular nucleus Ventroposterior lateral nucleus ; Inhibition Tonic activation ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thalamic reticular nucleus (RTN) exerts an inhibitory influence upon the dorsal thalamus. During wakefulness and arousal, RTN neurons fire tonically, whereas during slow-wave sleep they fire rhythmic high frequency bursts. The effects produced by RTN inhibition upon the activity of dorsal thalamic neurons will therefore vary in relation to the firing mode of the RTN neurons. In the present study, we compared the effects of oscillating RTN neurons and of RTN neurons tonically activated with glutamate on the response profiles of single units reacting to controlled cutaneous stimulation in cat ventroposterior lateral thalamic nucleus (VPL). Experiments were performed under light barbiturate anesthesia and prior to the glutamate activation of the RTN, both RTN and VPL neurons showed spontaneous bursting patterns of activity consistent with the oscillatory mode. Typically, a cutaneous stimulus evoked a short latency excitatory response in VPL followed by a period of complete inhibition termed post-stimulus inhibition (PSI). In many neurons, the PSI was followed by a period of increased activity termed post-inhibitory excitation (PIE). Ejection of glutamate in the identified somatosensory division of the RTN shifted the oscillatory firing of its neurons to a high tonic mode and usually resulted in a decrease in VPL neuronal activity. Significant variations were observed in the occurrence and the magnitude of the effects among the different components of neuronal activity examined. Tonic activation of the RTN resulted in a significant reduction of ON- and OFF-PIEs in 81% of cases (30/37) and of spontaneous activity in 67% (22/ 33). In contrast, the response to a cutaneous stimulus was decreased in only 29% of cases (17/59) and was significantly increased in 24% (14/59). Tonic activation of the RTN by glutamate resulted in little change in the firing pattern of VPL neurons, and both short and long spike intervals were affected in a similar proportion. We conclude that the components of VPL neuronal activity most affected by switching RTN neurons from the oscillatory to the tonic mode are those normally dependent upon RTN neuronal oscillation. The present results also suggest that lowering background activity, such as occurs during the transition from sleep to wakefulness, is a factor leading to increase in the responsiveness of dorsal thalamic neurons.
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  • 40
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    Keywords: Muscles ; Muscle contraction ; Motor unit ; Contractile properties ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The active length-tension curves of identified single motor units (MUs) belonging to peroneus longus muscle (PL) of anaesthetized adult cats were obtained by eliciting isometric single twitches and tetani. The recorded responses were evaluated by measuring the peak tension amplitude and the tension-time area at muscle lengths extending throughout the physiological length range of the muscle (mean 5.5 mm, standard deviation ±0.8). The muscle lengths at which each tested MU developed its maximal twitch (L tw) and tetanic (L te) tensions were determined and compared with the muscle length (L o) at which the stimulation of all the α-axons, innervating PL and contained in L7 ventral root, developed their maximal twitch tension. The mean of single MU L tw values was at L o+1.08±1.1 mm. Slow MUs showed the longest values of L tw(L o+1.6±1.0 mm). Single MUs stimulated at tetanic frequencies presented their L te at values shorter than L o (L o−2.8±1.7 mm). Slow MUs had the shortest L te (L o−3.4±1.5 mm). For all the units L te was shorter than L tw. L tw and L te were, respectively, negatively and positively correlated with the developed tension. Optimal length values also appeared to be related to the MU types. The possibility is discussed that the muscle and tendon compliances and the high non-linearities to the applied forces are the main factors which can determine the differences among L o, L tw and L te values. The relationships between MU type and optimal length values are suggested to be, at least partly, an epiphenomenon due to the different contraction strengths of the various MU types. However, the heterogeneous distribution of the MU types is brought into account to explain the dependence of L tw and L te values on MU type.
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  • 41
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    Experimental brain research 101 (1994), S. 397-405 
    ISSN: 1432-1106
    Keywords: Posture ; Quadrupedal stance ; Central set ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to examine the effect of prior experience concerning direction of a postural perturbation on the balance response of cats to translations of their support surface. Previous work has shown that, when cats are translated in many directions in the horizontal plane, they respond by exerting active forces with each paw in only two directions, termed the force constraint strategy. This study examined whether the force constraint strategy could be modified based on predictability of the direction of translation and whether this strategy is used by the naive animal with no prior experience of platform translation. Four cats were trained to stand quietly on the force platform using positive reinforcement, and then were implanted with chronically indwelling electrodes for recording electromyographic (EMG) activity. The first experiment concerned the response of the naive cats to their first exposure to platform translation and consisted of translations presented randomly in four different directions in the horizontal plane. The second experiment consisted of two complete sets of 16 directions of translation (15 trials per direction), with the direction of translation randomized in one set and serially ordered in the other, to make the direction of translation unpredictable or predictable, respectively. Forces exerted by the cat, EMG activity, and platform position were recorded during the 1-s trials. The use of the force constraint strategy was independent of prior experience with direction of translation, as was the amplitude of the response. Moreover, this strategy was observed in the naive cat. These findings suggest that the force constraint is a robust and consistent response to translational perturbations of stance in the cat and is part of its natural behavioral repertoire. The accuracy in specification of the direction of a postural response must be based on the sensory information that is obtained within a very short time after the onset of platform acceleration (loop time 40–70 ms). On the other hand, the amplitude of the postural response tended to decrease with experience and practice, suggesting a long-term change in central set that may manifest as a reduction in sensorimotor gain.
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  • 42
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    Experimental brain research 101 (1994), S. 375-384 
    ISSN: 1432-1106
    Keywords: Lateral cervical nucleus ; Ascending projections ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extracellular microelectrode recordings were made from single cells of the lateral cervical nucleus (LCN) in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The cells were tested for antidromic activation from the contralateral medial lemniscus and the contralateral tectum. Seventytwo LCN units were recorded which projected to one or both targets. Sixty (83%) projected through the medial lemniscus, and of these 36 (50% of the total) also projected to the tectum, whereas 24 (33%) projected through the medial lemniscus only; 12 (17%) projected only to the tectum. Twenty-nine units (40%) were excited by moving hairs of the coat but not by pinch of the skin, and 9 (31%) of these projected to the tectum, 11 (38%) through the medial lemniscus and 9 (31%) to both targets. Forty units (56%) were excited by hair movement and noxious pinch, and 3 (7%) of these projected to the tectum, 10 (25%) through the medial lemniscus and 27 (68%) to both targets. Three units (4%) had no discernible receptive fields and they all projected through the medial lemniscus, but not to the tectum. Of the 12 units projecting only to the tectum, 11 had receptive fields completely or partially on the trunk. Units projecting either through the medial lemniscus only, or through the medial lemniscus and also into the tectum, had receptive fields more widely distributed: these included small fields on the fore- and hind feet, on the limbs and also, a minority, on the trunk. Units with glove- or stocking-like receptive fields projected through the medial lemniscus. The results show that while most LCN cells project through the medial lemniscus, those excited by hair movement alone preferentially project either to the tectum or through the medial lemniscus, but not by both routes. The differences in receptive field properties of the differently projecting units are discussed in terms of the possible functions of the spinocervical system.
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  • 43
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    Experimental brain research 101 (1994), S. 415-426 
    ISSN: 1432-1106
    Keywords: Visual cortex ; Orientation selectivity ; GABA inhibition ; Interlaminar connections ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intracortical inhibition is believed to enhance the orientation tuning of striate cortical neurons, but the origin of this inhibition is unclear. To examine the possible influence of ascending inhibitory projections from the infragranular layers of striate cortex on the orientation selectivity of neurons in the supragranular layers, we measured the spatiotemporal response properties of 32 supragranular neurons in the cat before, during, and after neural activity in the infragranular layers beneath the recorded cells was inactivated by iontophoretic administration of GABA. During GABA iontophoresis, the orientation tuning bandwidth of 15 (46.9%) supragranular neurons broadened as a result of increases in response amplitude to stimuli oriented about ±20° away from the preferred stimulus angle. The mean (±SD) baseline orientation tuning bandwidth (half width at half height) of these neurons was 13.08±2.3°. Their mean tuning bandwidth during inactivation of the infragranular layers increased to 19.59±2.54°, an increase of 49.7%. The mean percentage increase in orientation tuning bandwidth of the individual neurons was 47.4%. Four neurons exhibited symmetrical changes in their orientation tuning functions, while 11 neurons displayed asymmetrical changes. The change in form of the orientation tuning functions appeared to depend on the relative vertical alignment of the recorded neuron and the infragranular region of inactivation. Neurons located in close vertical register with the inactivated infragranular tissue exhibited symmetric changes in their orientation tuning functions. The neurons exhibiting asymmetric changes in their orientation tuning functions were located just outside the vertical register. Eight of these 11 neurons also demonstrated a mean shift of 6.67±5.77° in their preferred stimulus orientation. The magnitude of change in the orientation tuning functions increased as the delivery of GABA was prolonged. Responses returned to normal approximately 30 min after the delivery of GABA was discontinued. We conclude that inhibitory projections from neurons within the infragranular layers of striate cortex in cats can enhance the orientation selectivity of supragranular striate cortical neurons.
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  • 44
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    Experimental brain research 102 (1994), S. 181-197 
    ISSN: 1432-1106
    Keywords: Cross-correlation analysis ; Connection strength ; Somatosensory cortex ; Ventrobasal thalamus ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal responses to hairy skin stimulation were simultaneously recorded in the ventral posterolateral nucleus (VPL) of the thalamus and primary somatosensory cortex (SI) of halothane-anesthetized cats. Among 233 thalamocortical neuron pairs, cross-correlation analysis revealed significant interactions in 120 pairs. Excitatory interactions were most prevalent and included influences occurring exclusively in the thalamocortical (41 pairs) or corticothalamic (23 pairs) directions as well as multiphasic interactions (40 pairs) in both directions. Only 16 pairs exhibited inhibitory interactions and 7 of these involved multiphasic combinations of excitation and inhibition. In 14 of these neuron pairs, inhibition was exerted in the corticothalamic direction. Receptive field (RF) overlap between thalamic and cortical neurons varied considerably, and neuronal interactions were more likely for neuron pairs sharing large portions of their combined RFs. Computer-controlled stimulation was delivered to multiple RF sites but only 46% of the neuron pairs displayed interactions at more than one stimulation site and only four neuron pairs showed interactions at all stimulus positions. When interactions occurred at multiple stimulus sites, 40% of these interactions were characterized by timing shifts where the time interval between VPL and SI discharges varied as much as 20 ms because of stimulus relocation. In nine neuron pairs, systematic shifts in stimulus position produced reversals in the temporal sequence of thalamic and cortical neuronal discharges. Functional interactions between thalamic and cortical neurons were detected during both spontaneous and stimulus-induced activity. Matched-sample comparisons of connection strength and half-widths of thalamocortical peaks during spontaneous and stimulus-induced activity indicated that functional interactions produced by cutaneous stimulation were significantly stronger and had less temporal variability than those occurring spontaneously.
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  • 45
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    Experimental brain research 100 (1994), S. 1-6 
    ISSN: 1432-1106
    Keywords: Spinal cord ; Ascending tracts ; Spinocervical neurons ; Group II muscle afferents ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Peripheral input to spino-cervical tract (SCT) neurons located in the L4 and L5 segments of the cat spinal cord was investigated using both extracellular and intracellular recording. The main aim was to find out whether midlumbar SCT neurons are excited monosynaptically not only by cutaneous afferents but also by group II muscle afferents, as in the sacral segments but apparently not in the caudal lumbar segments. Input from group II muscle afferents was found in 73% of investigated neurons; the latencies of excitation by group II afferents were compatible with a monosynaptic coupling between these afferents and 62% of neurons. The majority of the midlumbar SCT neurons were excited by group II afferents of the quadriceps and deep peroneal nerves. The predominant monosynaptic input from cutaneous afferents to the same neurons was from the saphenous nerve.
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  • 46
    ISSN: 1432-1106
    Keywords: Posterior semicircular canal ; Vestibular nucleus neuron ; Medial mesodiencephalic junction ; Thalamus ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The axonal projections of 62 posterior canal (PC)-activated excitatory and inhibitory secondary vestibular neurons were studied electrophysiologically in cats. PC-related neurons were identified by monosynaptic activation elicited by electrical stimulation of the vestibular nerve and activation following nose-up rotation of the animal's head. Single excitatory and inhibitory neurons were identified by antidromic activation following electrical stimulation of the contralateral and ipsilateral medial longitudinal fasciculus, respectively. The oculomotor projections of identified neurons were confirmed with a spike-triggered averaging technique. The axonal projections of the identified neurons were then studied by systematic, antidromic stimulation of the mesodiencephalon. Excitatory neurons showed two main types of axonal projections. In one type, axonal branches were issued to the interstitial nucleus of Cajal, central gray, and thalamus including the ventral posterolateral, ventral posteromedial, ventral lateral, ventral medial, centromedian, central lateral, lateral posterior, and ventral lateral geniculate nuclei. The other type was more frequently observed, giving off axon collaterals to the above-mentioned regions and to Forel's field H as well. Inhibitory neurons issued axonal branches to limited areas which included the central gray, interstitial nucleus of Cajal, its adjacent reticular formation and caudalmost part of Forel's field H, but not the rostral part of the Forel's field H and the thalamus. These results suggest that PC-related excitatory neurons participate in the genesis of vertical eye movements and in the perception of the vestibular sensation, and that PC-related inhibitory neurons seem to take part only in the genesis of vertical eye movements.
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  • 47
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    Experimental brain research 101 (1994), S. 307-313 
    ISSN: 1432-1106
    Keywords: Perigeniculate nucleus ; X and Y cells ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The spike activity of perigeniculate cells evoked by small light spots flashing along the axes of their receptive fields was recorded and presented in response planes. This method allowed the investigated neurons to be grouped into two classes characterized by (1) large receptive fields and phasic-like responses and (2) small fields and tonic responses. The latency measurements for stimulation of the optic chiasma and visual cortex revealed that the cells from the first group are excited by fast, Y fibers and the second by slow, X axons. The spatial tuning curves of the second harmonic component, as measured from the responses of the cells from the two groups for slowly moving square gratings, are also different. We conclude that the X and Y systems of the visual pathway are segregated at the level of the perigeniculate nucleus.
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  • 48
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    Experimental brain research 102 (1994), S. 34-44 
    ISSN: 1432-1106
    Keywords: Fictive locomotion ; Scratch ; Flexor reflex afferents ; Group Ib ; Plateau potentials ; NMDA receptor ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lumbar motoneurones were recorded intracellularly during fictive locomotion induced by stimulation of the mesencephalic locomotor region in decerebrate cats. After blocking the action potentials using intracellular QX-314, and by using a discontinuous current clamp, it is shown that the excitatory component of the locomotor drive potentials behaves in a voltage-dependent manner, such that its amplitude increases with depolarisation. As the input to motoneurones during locomotion is comprised of alternating excitation and inhibition, it was desirable to examine the excitatory input in relative isolation. This was accomplished in spinalised decerebrate cats treated with nialamide and l-dihydroxy-phenylalanine (l-DOPA) by studying the excitatory post-synaptic potentials (EPSPs) evoked from the “flexor reflex afferents” (FRA) and extensor Ib afferents, both of which are likely to be mediated via the locomotor network. As expected, these EPSPs also demonstrate a voltage-dependent increase in amplitude. In addition, the input to motoneurones from the network for scratching, which is thought to share interneurones with the locomotor network, also results in voltage-dependent excitation. The possible underlying mechanisms of NMDA-mediated excitation and plateau potentials are discussed:both may contribute to the observed effect. It is suggested that this nonlinear increase in excitation contributes to the mechanisms involved in the production of the high rates of repetitive firing of motoneurones typically seen during locomotion, thus ensuring appropriate muscle contraction.
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  • 49
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    Experimental brain research 102 (1994), S. 69-74 
    ISSN: 1432-1106
    Keywords: Motoneurone ; Recruitment ; Force modulation ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the context of an analysis concerning factors of importance for the relative contributions of recruitment and rate gradation of muscle force, the distribution of electrical excitability was analyzed for medial gastrocnemius (MG) motoneurones of rat and cat. The experimental data came from previously collected intracellular measurements in animals anaesthetized with pentobarbitone. Electrical excitability was measured as the threshold (nanoamperes) for single spike generation (rheobase) in rat and for maintained repetitive firing (rhythmic threshold) in cat. Furthermore, the data included measurements of axonal conduction velocity and of contractile properties of the muscle units innervated by the studied motoneurones. The units were categorized into types S (slow-twitch, fatigue-resistant), FR (fast-twitch, fatigue-resistant) and FF (fast-twitch, fatiguable) on the basis of the combined criteria of twitch-speed and sensitivity to fatigue. We confirmed that, in spite of the presence of normal-looking symmetrical distributions of axonal conduction velocity, there was a positive skew in the distribution of electrical excitability (relatively high numbers of cells with low thresholds, few with high ones). Within each unit category (S, FR, FF), we ranked the motoneurones according to their relative electrical excitability and calculated the threshold difference between consecutive cells (“threshold spacing”). In accordance with the skewed distribution of electrical excitability, we found that the mean threshold spacing was ranked in the same way as the mean thresholds, i.e. S〈FR〈FF; the statistical analysis showed that, for cats as well as rats, small threshold-spacing steps were significantly more common for S than for FF motoneurones. In the discussion it is pointed out that the narrow threshold-spacing for S units, as compared to FF units, would tend to decrease the relative amount of recruitment-parallel rate modulation in these cells. Thus, the spacing of recruitment thresholds tends to allow the easily recruited S motoneurones to remain firing at relatively low rates during ongoing recruitment gradation, which would be of potential value in promoting a high degree of endurance for long-lasting postural contractions.
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  • 50
    ISSN: 1432-2072
    Keywords: Zolpidem ; EEG ; Non benzodiazepine hypnotic ; Clinical pharmacology ; Healthy volunteers ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Zolpidem is an imidazopyridine which binds specifically to the ω1 receptor. Zolpidem demonstrated potent hypnotic activity at a dose of 10 mg. Pharmacodynamics and pharmacokinetics of zolpidem were studied after daytime administration in a randomised, double-blind, placebo-controlled, cross-over trial. Single doses of zolpidem (10 mg IV as a 3-min infusion and 20 mg orally) and placebo were firstly tested in 12 healthy young male volunteers. Two other doses (5 mg IV and orally) were then evaluated in 6 out of these 12 subjects. EEG (4 leads = Fp2-T4, Fp1-T3, T4-02 and T3-01), and Stanford Sleepiness Scale (SSS) were measured up to 5 h post-dosing. Blood samples were also collected up to 24 h. The time course of the hypnotic activity of zolpidem, assessed by the score obtained on SSS, showed a similar profile whatever the route or the dose administered: slightly earlier onset after IV but sedative scores were reached at 30 min and the effect peaked between 1 and 1.5 h and lasted 4 h in both conditions. The EEG profile of zolpidem was characterised by a decrease of alpha activity and an increase in delta and in beta activity. The effect on beta activity was marked within the first hour and then disappeared. The time course of delta and alpha activities indicated a rapid onset (10 min after IV, 30 min after oral route) and a duration of 3–4 h. The amplitude of these relative EEG changes and their duration were independent of the route of administration and the dose administered. AUC and Cmax increased proportionally to the administered dose and elimination half life (2 h), clearance and volume of distribution did not change according to the dose or the route of administration. Tmax was 1 h after the oral administration. The absolute bioavailability was about 70%. In conclusion, EEG induced changes and score of SSS were in good correlation with what has been observed with insomniac patients: zolpidem has a rapid onset and a short duration of action.
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  • 51
    ISSN: 1432-2072
    Keywords: Social phobia ; Psychopharmacology ; Serotonin reuptake inhibitors ; Fluvoxamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown selective and non-selective monoamine oxidase inhibitors (MAOIs) to be effective in the treatment of social phobia. In this study we investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in social phobia. Thirty patients with social phobia (DSM-IIIR) were treated with the SSRI fluvoxamine (150 mg daily) using a 12-week double-blind placebo controlled design. A substantial improvement was observed in seven (46%) patients on fluvoxamine and in one (7%) on placebo. Statistically significant effects were seen on measures of social anxiety and general (or anticipatory) anxiety in patients treated with fluvoxamine compared with placebo. The level of phobic avoidance decreased also but the difference at endpoint between fluvoxamine and placebo failed to reach statistical significance. It is concluded that treatment with the SSRI fluvoxamine has beneficial effects in patients suffering from social phobia, suggesting that serotonergic mechanisms might be implicated in social anxiety.
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  • 52
    ISSN: 1432-2013
    Keywords: Blood-brain barrier ; Intravital fluorescence microscopy ; Computerised image analysis ; FITC-dextran ; Hypercapnia ; Adenosine ; Cerebral blood vessels ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present paper describes a new method using computerised image analysis techniques for quantification of tracer extravasation over the blood-brain barrier as studied by intravital fluorescence microscopy. Cats were equipped with an open cranial window and continuously infused with fluorescein isothiocyanate-labelled dextran (FITC-dextran, mol. wt. 70 000) to maintain a steady plasma concentration. Several cortical fields were recorded in each experiment and the images stored on video tape for off-line analysis. This procedure, which largely eliminates the superficial pial vasculature and allows extraction of the extravasation areas, consists of the following steps: (1) averaging of images, (2) software shading correction based on the original images for compensation of optical non-uniformity, (3) correction of displacement artefacts, (4) intensity adjustment, (5) generation of subtraction images by subtracting the first image of a series from the subsequent ones, (6) median filtering and thresholding, (7) a length recognition algorithm, and (8) elimination of small areas. Compared to the previously described method, step (2) has been newly developed and steps (4) and (8) added to enhance sensitivity for detecting tracer extravasation. The degree of extravasation in a cortical field at a given time point [E(f) value] was calculated as the mean intensity of the remaining pixels. TheE(f) is a quantitative value computed by a fully automatised procedure which takes into account the number, as well as the size and intensity, of extravasation areas in a given cortical field. TheE(f) values obtained at different times in a series of experiments were averaged to give theE(I) value. TheE(I) value did not alter when hypercapnia was employed to induce pure vasodilatation. On the other hand it increased dramatically, indicating tracer extravasation, during topical application of high concentrations of adenosine (10−5–10−3 M). The new computerised image analysis procedure may therefore be suitable for measuring quantitatively tracer extravasation over the blood-brain barrier in vivo under different experimental conditions. It may also be applicable to study changes of vascular permeability in peripheral vascular beds.
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  • 53
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    Astrophysics and space science 216 (1994), S. 153-154 
    ISSN: 1572-946X
    Keywords: Chemistry ; Molecular Hydrogen ; Cloud Models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Observations of the CO J=1-0 line are commonly used as a tracer for molecular material in clouds. The ratio of the H2 column density to the integrated intensity of this line,X, is often taken to be constant, despite theoretical and observational uncertainty. We have tried to identify how this ratio depends on cloud parameters, testing a simple theoretical argument suggesting its invariance with respect to density. The apparent constancy can be understood if clouds are clumpy on scales of Av ≈ 1-2 mag.
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  • 54
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    Pflügers Archiv 426 (1994), S. 304-309 
    ISSN: 1432-2013
    Keywords: Mechanoreceptors ; Cat ; Urinary bladder ; Functional properties ; Bladder pressure ; Wall tension ; Natural distension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bladder wall mechanoreceptors are essential elements in micturition and continence reflexes. While they have been described as tension receptors, their response to bladder wall deformation has always been characterised in terms of pressure. The firing patterns of 10 bladder wall mechanoreceptors were determined during bladder distensions at a natural and a much faster rate. In all units firing rate was higher at any given pressure at the slower bladder distension rate. This inverse rate dependence was reduced when firing rate was related to a derived measure of bladder wall tension and abolished when multi-fibre recordings were used. We conclude that it is important to incorporate volume effects in studies of continence control systems.
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  • 55
    ISSN: 1432-2013
    Keywords: Sympathetic nerve stimulation ; Small pulmonary vessels ; Selective arterial vasoconstriction ; α-Adrenergic receptors ; β-Adrenergic receptors ; Flow velocity ; Volume flow ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using an X-ray television system, we measured directly changes in the internal diameter (ID), flow velocity, and volume flow of the small pulmonary vessels (100–500 μm ID) in response to electrical sympathetic nerve stimulation (SNS) in anaesthetized cats before and after adrenergic receptor blockade. Flow velocity was obtained by measuring the distance that the leading edge of the contrast medium moved per 0.1 s in the small arteries. Volume flow was obtained from the product of flow velocity and cross-sectional area calculated from the ID of the small arteries. SNS was accolmplished with 10- to 15-V square-wave pulses of 2-ms duration at 20–30 Hz for 20-s periods. In response to SNS, arterial ID decreased significantly by 8–13% in the 200- to 500-μm vessels but not in the 100- to 200-μm vessels. In the veins, on the other hand, there was no significant ID decrease in any of the 100- to 500-μm vessels. After α-receptor blockade (phentolamine, 2 mg/kg i.V.), there were significant ID increases (4–9%) in the 100- to 500-μm arteries in response to SNS, the maximum increases being in the 100- to 200-μm arteries. After β-blockade (propranolol, 2 mg/kg i.V.), the ID decrease due to SNS in the 200- to 500-μm arteries was enhanced (24–27%) and, in addition, the 100- to 200-μm arteries exhibited a significant ID decrease (18%). Combined α and β-blockade completely abolished the ID decrease due to SNS. In the veins, on the other hand, no ID change occurred even after α- or β-blockade. The results indicate that SNS selectively constricts 200- to 500-μm arteries. The data suggests that SNS has α-mediated vasoconstrictor and β-mediated vasodilator effects on the 100- to 500-μm arteries and that the ID response pattern to SNS depends chiefly on the balance between α-mediated vasoconstriction and β-mediated vasodilation. Associated with the ID decrease due to SNS, flow velocity was increased by 21%. However, SNS did not affect volume flow, because the increase in velocity was compensated by the reduction in the cross-sectional area (due to the decreased ID).
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  • 56
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    European archives of oto-rhino-laryngology and head & neck 251 (1994), S. 117-118 
    ISSN: 1434-4726
    Keywords: Autonomic nervous system ; Tongue ; Horseradish peroxidase ; Neural tracer ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Autonomic innervation of the tongue was investigated in cats using the horseradish peroxidase retrograde tracing method. The tongue was found to be innervated by sympathetic fibers originating in the ipsilateral superior cervical ganglion, but not by those originating in the middle cervical ganglion or stellate ganglion. The tongue was also innervated by fibers originating in the ipsilateral pterygopalatine ganglion, suggesting that this innervation is parasympathetic.
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  • 57
    ISSN: 1573-739X
    Keywords: Antimalarials ; Artemisia annua L ; Artemisinin ; Biosynthesis ; Chemistry ; Clinical trials ; Pharmacology ; Phytochemistry ; Sesquiterpenes ; Toxicology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Artemisinin, a sesquiterpene lactone endoperoxide isolated fromArtemisia annua L., and a number of its semisynthetic derivatives have shown to possess antimalarial properties. They are all eflective againstPlasmodium parasites that are resistant to the newest and commonly used antimalarial drugs. This article gives a survey of the literature dealing with artemisinin-relaled antimalarial issues that have appeared from the end of 1989 up to the beginning of 1994. A broad range of medical and pharmaceutical disciplines is covered, including phytochemical aspects like the selection of high-producing plants, analytical procedures, and plant biotechnology. Furthermore, the organic synthesis of artemisinin derivatives is discussed, as well as their mechanism of action and antimalarial activity, metabolism and pharmacokinetics, clinical studies, sideeffects and toxicology, and biological activities other than antimalarial activity.
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  • 58
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    Journal of Chemometrics 8 (1994), S. 21-36 
    ISSN: 0886-9383
    Keywords: GRAM ; Tucker ; Unfold ; NBRA ; Second-order ; Three-way ; PARAFAC ; Trilinear ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: If an analytical instrument or instrumental method gives a response matrix when analyzing a pure analyte, the instrument or instrumental method is called a second-order method. Second-order methods that generate a response matrix for a pure analyte of rank one are called rank-one second-order methods. If the response matrix of a pure analyte is not rank one, essentially two cases exist: medium rank (between two and five) and high rank (greater than five). Subsequently, medium- and high-rank second-order calibration tries to use medium- and high-rank second-order methods to analyze for analytes of interest in a mixture. A particular advantage of second-order methods is the ability to analyze for analytes of interest in a mixture which contains unknown interferences. Keeping this advantage is the challenge on moving away from rank-one second-order calibration methods. In this paper a medium-rank second-order calibration method is proposed based on least-squares restricted Tucker models. With this method the second-order advantage is retained.
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  • 59
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    Journal of Chemometrics 8 (1994), S. 81-93 
    ISSN: 0886-9383
    Keywords: Sensory evaluation ; Cumulative ranks ; Assessor variation ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A graphical method of assessing differences between sets of rankings based on cumulative ranks is developed. The method can be used to identify rankings that differ over all or just part of the range of objects ranked. The method is applied to an example of sensory evaluation of green peas in which ten assessors scored six attributes on each of 60 samples.
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  • 60
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    Journal of Chemometrics 8 (1994), S. i 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 61
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    Journal of Chemometrics 8 (1994), S. 155-168 
    ISSN: 0886-9383
    Keywords: Trilinear models ; Tensorial resolution ; PARAFAC ; Swamps ; Two-factor degeneracy ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The alternating least squares PARAFAC algorithm is a useful tool for resolving trilinear three-way data arrays. Occasionally, however, it becomes bogged down for many iterations in the vicinity of a poor quality resolution before moving on to a much superior optimum fit. We investigate this behavior in a simulation study and suggest ways of overcoming the obstacles it presents.
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  • 62
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 63
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    Journal of Chemometrics 8 (1994), S. i 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 64
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    Journal of Chemometrics 8 (1994), S. 181-203 
    ISSN: 0886-9383
    Keywords: RAFA ; GRAM ; Eigenvalues ; Bias ; Variance ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rank annihilation factor analysis (RAFA) is a method for multicomponent calibration using two data matrices simultaneously, one for the unknown and one for the calibration sample. In its most general form, the generalized rank annihilation method (GRAM), an eigenvalue problem has to be solved. In this second paper expressions are derived for predicting the bias and variance in the eigenvalues of GRAM. These expressions are built on the analogies between a reformulation of the eigenvalue problem and the prediction equations of univariate and multivariate calibration. The error analysis will also be performed for Lorber's formulation of RAFA. It will be demonstrated that, depending on the size of the eigenvalue, large differences in performance must be expected. A bias correction technique is proposed that effectively eliminates the bias if the error in the bias estimate is not too large. The derived expressions are evaluated by Monte Carlo simulations. It is shown that the predictions are satisfactory up to the limit of detection. The results are not sensitive to an incorrect choice of the dimension of the factor space.
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  • 65
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    Journal of Chemometrics 8 (1994), S. 301-302 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 66
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    Journal of Chemometrics 8 (1994) 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 67
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    Journal of Chemometrics 8 (1994), S. 305-331 
    ISSN: 0886-9383
    Keywords: Pyrolysis ; Mass spectroscopy ; Multivariate analysis ; Biological material identification ; Convexity ; Cones ; Subspaces ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This work addresses the classification of high-dimensional time-dependent pyrolysis mass spectra of biological samples. The aim was the detection and classification of biological agents, and the developed approach resembles mixture analysis. The data were projected on to a low-dimensional subspace using singular value decomposition. Then a convex cone was formed on this subspace, showing as its corners physically meaningful components of the sample. This technique enabled separation of a biological material signal largely independent of the absolute amount of sample. The detection of the presence of any biological material could be accomplished based on the convex cone alone, without other reference to the mass spectra. Automated clustering of samples was successfully carried out using a minimal spanning tree.
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  • 68
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    Journal of Chemometrics 8 (1994), S. 373-373 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 69
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    Journal of Chemometrics 8 (1994) 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 70
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    Journal of Chemometrics 8 (1994), S. 37-44 
    ISSN: 0886-9383
    Keywords: Bootstrap ; Confidence interval ; Non-linear regression ; Monte Carlo methods ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Non-linear regression models describing the toxicity of a mixture of rotenone and pyrethrins as an insecticide, the catalytic dehydration of n-hexyl alcohol and the Michaelis-Menten model for characterizing reaction rates in enzyme systems will be used to illustrate the accuracy of bootstrap methods in non-linear regression. Classical and bootstrap confidence intervals for the parameter estimates will be presented.
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  • 71
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 72
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    Journal of Chemometrics 8 (1994), S. 102-102 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 73
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    Journal of Chemometrics 8 (1994), S. 111-125 
    ISSN: 0886-9383
    Keywords: PLS regression algorithm ; Kernel ; Many-variable data sets ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A fast PLS regression algorithm dealing with large data matrices with many variables (K) and fewer objects (N) is presented For such data matrices the classical algorithm is computer-intensive and memory-demanding. Recently, Lindgren et al. (J. Chemometrics, 7, 45-49 (1993)) developed a quick and efficient kernel algorithm for the case with many objects and few variables. The present paper is focused on the opposite case, i.e. many variables and fewer objects. A kernel algorithm is presented based on eigenvectors to the ‘kernel’ matrix XX TYYT, which is a square, non-symmetric matrix of size N × N, where N is the number of objects. Using the kernel matrix and the association matrices XXT (N × N) and YYT (N × N), it is possible to calculate all score and loading vectors and hence conduct a complete PLS regression including diagnostics such as R2. This is done without returning to the original data matrices X and Y. The algorithm is presented in equation form, with proofs of some new properties and as MATLAB code.
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  • 74
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    Journal of Chemometrics 8 (1994), S. 169-174 
    ISSN: 0886-9383
    Keywords: Kernel algorithm ; PLS ; SVD ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Lindgren et al. (J. Chemometrics, 7, 45-49 (1993)) published a so-called kernel algorithm for PLS regression of Y against X when the number of objects is very large. The algorithm is based solely on deflation of the cross-product matrices XTX, YTY and XTY. The algorithm is now described in a shorter and more transparent way and compared with a similar algorithm for the singular value decomposition of XTY.
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  • 75
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    Journal of Chemometrics 8 (1994) 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 76
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    Journal of Chemometrics 8 (1994), S. 241-241 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 77
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    Journal of Chemometrics 8 (1994), S. 273-285 
    ISSN: 0886-9383
    Keywords: GRAM ; Least-squares problem ; Eigenvalue problem ; NIPALS ; Performance index ; Condition number ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In this paper we discuss the practical implementation of the generalized rank annihilation method (GRAM). The practical implementation comes down to developing a computer program where two critical steps can be distinguished: the construction of the factor space and the oblique rotation of the factors. The construction of the factor space is a least-squares (LS) problem solved by singular value decomposition (SVD), whereas the rotation of the factors is brought about by solving an eigenvalue problem. In the past several formulations for GRAM have been published. The differences essentially come down to solving either a standard eigenvalue problem or a generalized eigenvalue problem. The first objective of this paper is to discuss the numerical stability of the algorithms resulting from these formulations. It is found that the generalized eigenvalue problem is only to be preferred if the construction of the factor space is not performed with maximum precision. This is demonstrated for the case where the dominant factors are calculated by the non-linear iterative partial least-squares (NIPALS) algorithm. Several performance measures are proposed to investigate the numerical accuracy of the computed solution. The previously derived bias and variance are proposed to estimate the number of physically significant digits in the computed solution. The second objective of this paper is to discuss the relevance of theoretical considerations for application of GRAM in the presence of model errors.
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    Journal of Chemometrics 8 (1994), S. 299-301 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    Journal of Chemometrics 8 (1994), S. i 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 80
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    Journal of Chemometrics 8 (1994), S. 349-363 
    ISSN: 0886-9383
    Keywords: Variable selection ; PLS ; Calibration ; Modelling ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A modified PLS algorithm is introduced with the goal of achieving improved prediction ability. The method, denoted IVS-PLS, is based on dimension-wise selective reweighting of single elements in the PLS weight vector w. Cross-validation, a criterion for the estimation of predictive quality, is used for guiding the selection procedure in the modelling stage. A threshold that controls the size of the selected values in w is put inside a cross-validation loop. This loop is repeated for each dimension and the results are interpreted graphically. The manipulation of w leads to rotation of the classical PLS solution. The results of IVS-PLS are different from simply selecting X-variables prior to modelling. The theory is explained and the algorithm is demonstrated for a simulated data set with 200 variables and 40 objects, representing a typical spectral calibration situation with four analytes. Improvements of up to 70% in external PRESS over the classical PLS algorithm are shown to be possible.
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  • 81
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    Journal of Chemometrics 8 (1994), S. i 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 82
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    Journal of Chemometrics 8 (1994), S. 409-421 
    ISSN: 0886-9383
    Keywords: Deconvolution ; FT-IR spectroscopy ; Protein conformations ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In a variety of spectroscopic techniques the fundamental problem exists of determination of the individual spectral components, intrinsically overlapped in the measured spectrum. This is a typical deconvolution problem and several methods and techniques have been proposed for its solution in the technical literature, but suggestions of new approaches are still of interest. A new deconvolution procedure is presented here based on the use of the conjugate gradient minimization algorithm with the addition of sutiable constraints directly obtained by the application to the measured spectrum of the second-derivative operator or more sophisticated resolution enhancement procedures. Since in the examined case deconvolution essentially requires the minimization of a non-convex function, the use of such constraints is extremely important to supply suitable input parameters to the conjugate gradient algorithm to avoid obtaining minimum points which have no physical meaning. In our case each spectral compoent used for deconvolution has been assumed to have a Gaussian analytical definition fully identified by three parameters (amplitude, central frequency, spectral bandwidth), so that the input values required to start the deconvolution process are the number M of Gaussian components and 3M suitable initial approximations of the parameters above. It is shown that all this information can be obtained from the measured data. The deconvolution procedure was implemented by a FORTRAN Microsoft Version 5.1 program and experimental results relative to spectroscopic data obtained by FT-IR analysis of human serum albumin are reported. The results are discussed and compared with data obtained by the use of other techniques.
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  • 83
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 84
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    Journal of Chemometrics 8 (1994), S. i 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 85
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 1-3 
    ISSN: 0887-3585
    Keywords: protein folding ; protein conformation ; Paracelsus award ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
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  • 86
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 4-13 
    ISSN: 0887-3585
    Keywords: trichosanthin ; ribosome-inactivating proteins ; crystal structure ; orthorhombic ; molecular replacement ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Trichosanthin (TCS) is one of the single chain ribosome-inactivating proteins (RIPs). The crystals of the orthorhombic form of trichosanthin have been obtained from a citrate buffer (pH 5.4) with KC1 as the precipitant. The crystal belongs to the space group P212121 with a = 38.31, b = 76.22, c = 79.21 Å. The structure was solved by molecular replacement method and refined using the programs XPLOR and PROLSQ to an R-factor of 0.191 for the reflections within the 6-1.88 Å resolution range. The bond length and bond angle in the protein molecule have root-mean-square deviations from ideal value of 0.013 Å and 3.3°, respectively. The refined model includes 247 residues and 197 water molecules. The TCS molecule consists of two structural domains. The large domain contains six α-helices, a six stranded sheet, and an antiparallel β-sheet. The small domain has a largest α-helix, which shows a distinct bend. The possible active site of the molecule located on the cleft between two domains was proposed. In the active site Arg-163 and Glu-160, Glu-189 and Arg-122 form two ion pairs, Glu-189 and Gln-156 are hydrogen bonded to each other. Three water molecules are bonded to the residues in the active site region. The structures of TCS molecule and ricin A-chain (RTA) superimpose quite well, showing that the structures of the two protein molecules are homologous. Comparison of the structures of the TCS molecule in this orthorhombic crystal with that in the monoclinic crystal indicates that there are no essential differences of the structures between the two protein crystals. © 1994 Wiley-Liss, Inc.
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  • 87
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 80-83 
    ISSN: 0887-3585
    Keywords: maize protein ; crystals ; X-ray diffraction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Phospholipid transfer protein from maize seedlings has been crystallized using trisodium citrate as precipitant. The crystal belongs to the orthorhombic space group P212121 with unit cell dimensions of a = 24.46 Å, b = 49.97 Å, and c = 69.99 Å. The presence of one molecule in the asymmetric unit gives a crystal volume per protein mass (Vm) of 2.36 Å 3/Da and a solvent content of 48% by volume. The X-ray diffraction pattern extends at least to 1.6 Å Bragg spacing when exposed to both CuKα and synchrotron X-rays. A set of X-ray data to approximately 1.9 Å Bragg spacing has been collected from a native crystal. © 1994 Wiley-Liss, Inc.
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  • 88
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 85-97 
    ISSN: 0887-3585
    Keywords: protein conformation ; secondary structure ; protein folding ; helix stability ; helix formation ; conformational entropy ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Much effort has been invested in seeking to understand the thermodynamic basis of helix stability in both peptides and proteins. Recently, several groups have measured the helix-forming propensities of individual residues (Lyu, P. C., Liff, M. I., Marky, L. A., Kallenbach, N. R. Science 250:669-673, 1990; O'Neil, K. T., DeGrado, W. F. Science 250:646-651, 1990; Padmanabhan, S., Marqusee, S., Ridgeway, T., Laue, T. M., Baldwin, R. L. Nature (London) 344:268-270, 1990). Using Monte Carlo computer simulations, we tested the hypothesis that these differences in measured helix-forming propensity are due primarily to loss of side chain conformational entropy upon helix formation (Creamer, T. P., Rose, G. D. Proc. Natl. Acad. Sci. U.S.A. 89:5937-5941, 1992). Our previous study employed a rigid helix backbone, which is here generalized to a completely flexible helix model in order to ensure that earlier results were not a methodological artifact. Using this flexible model, side chain rotamer distributions and entropy losses are calculated and shown to agree with those obtained earlier. We note that the side chain conformational entropy calculated for Trp in our previous study was in error; a corrected value is presented. Extending earlier work, calculated entropy losses are found to correlate strongly with recent helix propensity scales derived from substitutions made within protein helices (Horovitz, A., Matthews, J. M., Fersht, A. R. J. Mol. Biol. 227:560-568, 1992; Blaber, M., Zhang, X.-J., Matthews, B. M. Science 260:1637-1640, 1993). In contrast, little correlation is found between these helix propensity scales and the accessible surface area buried upon formation of a model polyalanyl α-helix. Taken in sum, our results indicate that loss of side chain entropy is a major determinant of the helix-forming tendency of residues in both peptide and protein helices. © 1994 Wiley-Liss, Inc.
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  • 89
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 165-173 
    ISSN: 0887-3585
    Keywords: algoriths ; structure alignment ; Protein Data Bank ; protein superfamilies ; structural homology ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The number of protein structures known in atomic detail has increased from one in 1960 (Kendrew, J. C., Strandberg, B. E., Hart, R. G., Davies, D. R., Phillips, D. C., Shore, V. C. Nature (London) 185:422-427, 1960) to more than 1000 in 1994. The rate at which new structures are being published exceeds one a day as a result of recent advances in protein engineering, crystallography, and spectroscopy. More and more frequently, a newly determined structure is similar in fold to a known one, even when no sequence similarity is detectable. A new generation of computer algorithms has now been developed that allows routine comparison of a protein structure with the database of all known structures. Such structure database searches are already used daily and they are beginning to rival sequence database searches as a tool for discovering biologically interesting relationships. © 1994 Wiley-Liss, Inc.
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  • 90
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 199-221 
    ISSN: 0887-3585
    Keywords: multicopy simulation search ; rational drug design ; database search ; computer-aided design ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A program (HOOK) is described for generating potential ligands that satisfy the chemical and steric requirements of the binding region of a macromolecule. Functional group sites with defined positions and orientations are derived from known ligand structures or the multicopy simulation search (MCSS) method (Miranker, A., Karplus, M. Proteins 11:29-34, 1991). HOOK places molecular “skeletons” from a database into the protein binding region by making bonds between sites (“hooks”) on the skeleton and functional groups. The nonpolar interactions with the binding region of candidate molecules are assessed by use of a simplified van der Waals potential. The method is illustrated by constructing ligands for the sialic acid binding site of the hemagglutinin from the influenza A virus and the active site of chloramphenicol acetyltransferase. Aspects of the HOOK program that lead to a highly efficient search of 105 or more skeletons for binding to 102 or more functional group minima are outlined. © 1994 Wiley-Liss, Inc.
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  • 91
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 230-243 
    ISSN: 0887-3585
    Keywords: aspartate transcarbamylase ; multienzyme complex ; comparative structure modeling ; allosteric enzymes ; molecular evolution ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In Saccharomyces cerevisiae the first two reactions of the pyrimidine pathway are catalyzed by a multifunctional protein which possesses carbamylphosphate synthetase and aspartate transcarbamylase activities. Genetic and proteolysis studies suggested that the ATCase activity is carried out by an independently folded domain. In order to provide structural information for ongoing mutagenesis studies, a model of the three-dimensional structure of this domain was generated on the basis of the known X-ray structure of the related catalytic subunit from E. coli ATCase. First, a model of the catalytic monomer was built and refined by energy minimization. In this structure, the conserved residues between the two proteins were found to constitute the hydrophobic core whereas almost all the mutated residues are located at the surface. Then, a trimeric structure was generated in order to build the active site as it lies at the interface between adjacent chains in the E. coli catalytic trimer. After docking a bisubstrate analog into the active site, the whole structure was energy minimized to regularize the interactions at the contact areas between subunits. The resulting model is very similar to that obtained for the E. coli catalytic trimer by X-ray crystallography, with a remarkable conservation of the structure of the active site and its vicinity. Most of the interdomain and intersubunit interactions that are essential for the stability of the E. coli catalytic trimer are maintained in the yeast enzyme even though there is only 42% identity between the two sequences. Free energy calculations indicate that the trimeric assembly is more stable than the monomeric form. Moreover an insertion of four amino acids is localized in a loop which, in E. coli ATCase, is at the surface of the protein. This insertion exposes hydrophobic residues to the solvent. Interestingly, such an insertion is present in all the eukaryotic ATCase genes sequenced so far, suggesting that this region is interacting with another domain of the multifunctional protein. © 1994 Wiley-Liss, Inc.
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  • 92
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    Proteins: Structure, Function, and Genetics 19 (1994) 
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
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  • 93
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 273-276 
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
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  • 94
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    Proteins: Structure, Function, and Genetics 19 (1994), S. 302-309 
    ISSN: 0887-3585
    Keywords: dinuclear copper site ; hemocyanin ; oxygen binding ; allosteric regulation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The X-ray structure of an oxygenated hemocyanin molecule, subunit II of Limulus polyphemus hemocyanin, was determined at 2.4 Å resolution and refined to a crystallographic R-factor of 17.1%. The 73-kDa subunit crystallizes with the symmetry of the space group R32 with one subunit per asymmetric unit forming hexamers with 32 point group symmetry. Molecular oxygen is bound to a dinuclear copper center in the protein's second domain, symmetrically between and equidistant from the two copper atoms. The copper-copper distance in oxygenated Limulus hemocyanin is 3.6 ± 0.2 Å, which is surprisingly 1 Å less than that seen previously in deoxygenated Limulus polyphemus subunit II hemocyanin (Hazes et al., Protein Sci. 2:597, 1993). Away from the oxygen binding sites, the tertiary and quaternary structures of oxygenated and deoxygenated Limulus subunit II hemocyanins are quite similar. A major difference in tertiary structures is seen, however, when the Limulus structures are compared with deoxygenated Panulirus interruptus hemocyanin (Volbeda, A., Hol, W. G. J. J. Mol. Biol. 209:249, 1989) where the position of domain 1 is rotated by 8° with respect to domains 2 and 3. We postulate this rotation plays an important role in cooperativity and regulation of oxygen affinity in all arthropod hemocyanins. © 1994 Wiley-Liss, Inc.
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  • 95
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    Proteins: Structure, Function, and Genetics 20 (1994) 
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
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  • 96
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    Proteins: Structure, Function, and Genetics 20 (1994), S. 197-201 
    ISSN: 0887-3585
    Keywords: cytochrome P450 ; erythromycin ; P450eryF ; crystallization ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cytochrome P450eryF was overexpressed in Escherichia coli and purified in high yield. Crystals of the protein in the presence of the substrate, 6-deoxyerythronolide B, have been obtained by the hanging drop vapor diffusion method, using polyethylene glycol 4000 as a precipitant. The crystals belong to the orthorhombic space group P212121 with unit cell dimensions of a = 54.16 Å, b = 79.67 Å, and c = 99.48 Å and one molecule per asymmetric unit. A complete native data set has been collected to a resolution of 2.1 Å, and anomalous dispersion difference Patterson maps have revealed the location of the single heme iron atom. © 1994 Wiley-Liss, Inc.
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  • 97
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    Proteins: Structure, Function, and Genetics 20 (1994), S. 34-51 
    ISSN: 0887-3585
    Keywords: enzymology ; protein structure ; biochemical properties ; gene characterization ; bacterial diagnosis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Pyrrolidone carboxyl peptidase (EC 3.4.11.8) is an exopeptidase commonly called PYRase, which hydrolytically removes the pGlu from pGlu-peptides or pGlu-proteins.pGlu also known as pyrrolidone carboxylic acid may occur naturally by an enzymatic procedure or may occur as an artifact in proteins or peptides. The enzymatic synthesis of pGlu suggests that this residue may have important biological and physiological functions. Several studies are consistent with this supposition.PYRase has been found in a variety of bacteria, and in plant, animal, and human tissues For over two decades, biochemical and enzymatic properties of PYRase have been investigated. At least two classes of PYRase have been characterized. The first one includes the bacterial and animal type I PYRases and the second one the animal type II and serum PYRases. Enzymes from these two classes present differences in their molecular weight and in their enzymatic properties.Recently, the genes of PYRases from four bacteria, have been cloned and characterized, allowing the study of the primary structure of these enzymes, and their over-expression in heterelogous organisms. Comparison of the primary structure of these enzymes revealed striking homologies.Type I PYRases and bacterial PYRases are generally soluble enzymes, whereas type II PYRases are membrane-bound enzymes. PYRase II appears to play as important a physiological role as other neuropeptide degrading enzymes. However, the role of type I and bacterial PYRases remains unclear.The primary application of PYRase has been its utilization for some protein or peptide sequencing. Development of chromogenic substrates for this enzyme has allowed its use in bacterial diagnosis. © 1994 Wiley-Liss, Inc.
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  • 98
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    Proteins: Structure, Function, and Genetics 20 (1994), S. 52-67 
    ISSN: 0887-3585
    Keywords: nuclear magnetic resonance ; defensin ; hydrogen exchange ; antimicrobial peptides ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The exchange kinetics for the slowly exchanging amide hydrogens in three defensins, rabbit NP-2, rabbit NP-5, and human HNP-1, have been measured over a range of pH at 25°C using 1D and 2D NMR methods. These NHs have exchange rates 102 to 105 times slower than rates from unstructured model peptides. The observed distribution of exchange rates under these conditions can be rationalized by intramolecular hydrogen bonding of the individual NHs, solvent accessibility of the NHs, and local fluctuations in structure. The temperature dependencies of NH chemical shifts (NH temperature coefficients) were measured for the defensins and these values are consistent with the defensin structure. A comparison is made between NH exchange kinetics, NH solvent accessibility, and NH temperature coefficients of the defensins and other globular proteins. Titration of the histidine side chain in NP-2 was examined and the results are mapped to the three-dimensional structure. © 1994 Wiley-Liss, Inc.
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  • 99
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    Proteins: Structure, Function, and Genetics 18 (1994), S. 133-147 
    ISSN: 0887-3585
    Keywords: myoglobin ; simulation ; hydration ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An analysis of a molecular dynamics simulation of metmyoglobin in an explicit solvent environment of 3,128 water molecules has been performed. Both statics and dynamics of the protein-solvent interface are addressed in a comparison with experiment. Three-dimensional density distributions, temperature factors, and occupancy weights are computed for the solvent by using the trajectory coordinates. Analysis of the hydration leads to the localization of more than 500 hydration sites distributed into multiple layers of solvation located between 2.6 and 6.8 Å from the atomic protein surface. After locating the local solvent density maxima or hydration sites we conclude that water molecules of hydration positions and hydration sites are distinct concepts. Both global and detailed properties of the hydration cluster around myoglobin are compared with recent neutron and X-ray data on myoglobin. Questions arising from differences between X-ray and neutron data concerning the locations of the protein-bound water are investigated. Analysis of water site differences found from X-ray and neutron experiments compared with our simulation shows that the simulation gives a way to unify the hydration picture given by the two experiments. © 1994 John Wiley & Sons, Inc.
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  • 100
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    Proteins: Structure, Function, and Genetics 18 (1994), S. 119-132 
    ISSN: 0887-3585
    Keywords: electrostatics ; protein conformation ; DelPhi ; hydrophobicity ; RNase H ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In this paper we discuss the problem of including solvation free energies in evaluating the relative stabilities of loops in proteins. A conformational search based on a gas-phase potential function is used to generate a large number of trial conformations. As has been found previously, the energy minimization step in this process tends to pack charged and polar side chains against the protein surface, resulting in conformations which are unstable in the aqueous phase. Various solvation models can easily identify such structures. In order to provide a more severe test of solvation models, gas phase conformations were generated in which side chains were kept extended so as to maximize their interaction with the solvent. The free energies of these conformations were compared to that calculated for the crystal structure in three loops of the protein E. coli RNase H, with lengths of 7, 8, and 9 residues. Free energies were evaluated with a finite difference Poisson-Boltzmann (FDPB) calculation for electrostatics and a surface area-based term for nonpolar contributions. These were added to a gas-phase potential function. A free energy function based on atomic solvation parameters was also tested. Both functions were quite successful in selecting, based on a free energy criterion, conformations quite close to the crystal structure for two of the three loops. For one loop, which is involved in crystal contacts, conformations that are quite different from the crystal structure were also selected. A method to avoid precision problems associated with using the FDPB method to evaluate conformational free energies in proteins is described. © 1994 John Wiley & Sons, Inc.
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