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Notes: Summary 1. Interstitiospinal neurons were activated by antidromic stimulation of the ventromedial funiculus of the spinal cord at C1 and C4 in cerebellectomized cats under chloralose anesthesia. 46% of these neurons responded only at C1 (N cells) and the remaining 54% responded at C4 also (D cells). There is no topographical difference in the location of N and D cells. Conduction velocities of N cells were significantly slower than those of D cells. 2. Stimulation of the contralateral whole vestibular nerve evoked firing of 31% of both N and D cells; some responded early enough to suggest disynaptic connections, many responded late. Stimulation of the ipsilateral whole vestibular nerve evoked firing of several cells, one spontaneously discharging D cell was inhibited. 3. Stimulation of the contralateral individual semicircular canal nerves evoked firing of 33% of N cells and 13% of D cells. Most of these responses were late. N cells responded not only to the vertical canals but also to the horizontal canal, whereas D cells responded to the horizontal canal, but seldom to the vertical ones. Most canal responding neurons received specific input, only two N cells received convergent input from both the anterior and horizontal canals. Stimulation of the ipsilateral canals did not evoke excitation of any cells tested; one D cell was inhibited by stimulation of the horizontal canal nerve. 4. Stimulation of the rostral medial vestibular nucleus evoked characteristic negative field potentials centered in the contralateral interstitial nucleus of Cajal (INC). Approximately 60% of both N and D cells received excitation from the contralateral vestibular nuclei. About 17% of these responding neurons received monosynaptic excitation, most frequently from the rostral medial nucleus. Stimulation of the ipsilateral vestibular nuclei evoked firing of 12% of both N and D cells. 5. Twenty-nine neurons were fired antidromically by weak stimuli applied to the ipsilateral vestibular nuclei. Twenty-seven of the 29 were activated only from C1 and were found in the INC (10 cells) and in the reticular formation dorsal to the INC (19 cells). Measurement of the spread of the effect of stimulus current and comparison of latencies to stimulation of the vestibular nuclei and C1 indicated that these neurons have axon collaterals going to the ipsilateral vestibular nuclei. Only one of them received excitation from the contralateral posterior canal, others did not respond to the labyrinth. Some were activated by stimulation of the vestibular nuclei.

Notes: Summary 1. Experiments were performed in cats anesthetized with nitrous oxide to study the effects of INC lesions on responses of vestibular nuclear neurons during sinusoidal rotations of the head in the vertical (pitch) plane. Responses of neurons in the INC region were recorded during pitch rotations at 0.15 Hz. A great majority of these neurons did not respond to static pitch tilts, and they seemed to respond either to anterior or to posterior semicircular canal inputs with a peak phase lag of 140 deg (re head acceleration). 2. Responses of vestibular nuclei neurons in intact cats were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that seemed to respond to vertical semicircular canal inputs showed peak phase lags of 90 deg relative to head acceleration, whereas neurons that responded to static pitch tilts showed peak phase shifts near 0 deg. These results indicate that responses of neurons in the INC region lag those of vestibular neurons by about 50 deg, suggesting that the former neurons possess a phase-lagging (i.e. integrated) vestibular signal. 3. Responses of vestibular neurons in cats that had received electrolytic lesions of bilateral INCs 1–2 weeks previously were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that presumably responded to vertical semicircular canal inputs showed a peak phase lag of 60 deg relative to head acceleration, a significant decrease of the phase lag compared to normal, whereas responses near 0 deg were unchanged. Gain values of individual cells also significantly dropped from 2.07 ± 0.67 spikes · s−1/deg · s−22 (mean ± SD; normal cats) to 1.27 ± 0.68 spikes · s−2/deg · s−2 (INC lesioned cats) at 0.15 Hz. When responses of vestibular neurons were studied during pitch rotations in the range of 0.044–0.49 Hz in these cats, a large decrease of the phase lag was observed at lower frequencies, whereas the slopes of phase lag curves of vestibular neurons in intact cats were rather flat. 4. Procaine infusion into the bilateral INCs not only resulted in a decrease of 20–50 deg in the phase lag in responses of vestibular neurons that had lagged head acceleration by 90–140 deg before procaine infusion, but also dropped the gain of the response to rotation by an average of 31%, whereas responses of neurons that had showed phase shifts near 0 deg were not influenced consistently. Simultaneous recording of the vestibular neurons and the vertical vestibuloocular reflex (VOR) indicated that the phase advance and gain drop of vestibular neurons occurred earlier than those of the VOR. These results exclude the possibility that the change in dynamic response of vestibular neurons after procaine infusion is due to depression of general brain stem activity that may lead to the phase advance of the VOR, and suggest that the decrease of the phase lag and gain drop in responses of the vestibular neurons was caused by removal of the phase-lagging, feedback signal coming from the INC to the vestibular nuclei.

Notes: Summary (1) Experiments were performed in cats to examine effects of lesion of the interstitial nucleus of Cajal (INC) on head posture and the responsible pathway. Unilateral INC lesions resulted in lateral tilt of the head to the opposite side, and bilateral INC lesions resulted in dorsiflexion of the head as reported earlier. Such characteristic head posture was produced by successful kainic acid injections as well as by electrolytic lesions, suggesting that it was not due to damage of nerve fibers passing through the INC, but was produced most probably by damage of nerve cells in the INC. Electromyographic (EMG) recordings in unilateral INC-lesioned cats showed that activity was higher in the ipsilateral than in the contralateral major dorsal neck muscles (biventer, splenius, complexus, and rectus), and also higher in the contralateral than in the ipsilateral obliquus capitis caudalis muscle. The pattern of EMG activity was basically similar either when the cats presented typical head tilt or when their head was fixed to the frame at the stereotaxic plane. Characteristic head posture resulting from INC lesions seems consistent with the head posture produced by activation of these muscles. (2) Interruption of the medial and lateral vestibulospinal tracts did not significantly influence head tilt that had been produced by INC lesions. Characteristic head tilt was produced by INC lesions after cats had received bilateral labyrinthectomies, bilateral lesions of most of the vestibular nuclei, and bilateral aspiration of the cerebellar vermis and most of the lateral vestibular nuclei, indicating that typical head tilt can be produced without the vestibular nuclei and cerebellar vermis. (3) The medial longitudinal fasciculus (MLF) was interrupted at different levels to cut the major descending fibers from the INC. MLF interruption at the caudal midbrain produced typical head tilt, although MLF cut at the caudal pons and medulla was ineffective. Bilateral parasagittal cuts lateral to the MLF in the pons produced severe dorsiflexion of the head, and a subsequent unilateral INC lesion produced no further head tilt. These results suggest that fibers originating in the INC, removal of which is responsible for the typical head tilt, run through the MLF in the midbrain, and leave it in the pontine level. (4) After injections of HRP into the INC and closely surrounding reticular formation, anterogradely labeled fibers were seen in the ipsilateral rostral pontine MLF, and many of them entered the pontine reticular formation which corresponds to the caudal part of the nucleus reticularis (n.r.) pontis oralis and the rostral part of the n.r. pontis caudalis. In electrophysiological experiments, many neurons were antidromically activated in the INC region by weak stimuli confined to the ipsilateral rostral pontine reticular formation. Many cells were found within the INC and surrounding reticular formation. These results suggest that interruption of the INC projection to the rostral pontine reticular formation may be responsible for the characteristic head tilt produced by INC lesions.

Notes: Summary Recent studies have shown that the interstitial nucleus of Cajal (INC) in the midbrain reticular formation is involved in the conversion of vertical semicircular canal signals into eye position during vertical vestibuloocular reflexes. Secondary vestibulo-ocular relay neurons related to the vertical canals, which constitute the majority of output neurons sending signals from the vestibular nuclei directly to the oculomotor nuclei, have been shown to project axon collaterals to the region within and near the INC. To understand how the INC is involved in the signal conversion, latencies of response of neurons in the INC region to electrical stimulaton of the vestibular nerve were examined in alert cats. The responses of 96 cells whose activity was clearly modulated by sinusoidal pitch rotation (at 0.31 Hz) were analyzed. These included 41 cells whose activity was closely correlated with vertical eye movement (38 burst-tonic and 3 tonic neurons), and 55 other cells (called pitch cells as previously). Twenty nine of the 96 cells (30%) were activated at disynaptic latencies following single shock stimulation of the contralateral vestibular nerve. Disynaptically activated cells were significantly more frequent for pitch cells than for eye movement-related cells (25/55 = 45% vs 4/41 = 10%; p 〈 0.001, Chi-square test). Conversely, cells that did not receive short-latency activation (〈 6 ms) were more frequent among eye movement-related cells than pitch cells (26/41 = 63% vs 13/55 = 24%; p 〈 0.001, Chi-square test). Pitch cells showed significantly less phase lag (re head acceleration) than eye movement-related cells during sinusoidal pitch rotation (mean ± SD 124° ± 17° vs 138° ± 14°. p 〈 0.01, t-test). These results suggest that 1) cells in the INC region other than burst-tonic and tonic neurons mainly receive direct inputs from secondary vestibulo-ocular relay neurons, and that 2) vertical canal signals reach eye movement-related neurons mainly polysynaptically.

Notes: Summary 1. Maximal activation directions of vertical burst-tonic and tonic neurons in the region of the interstitial nucleus of Cajal (INC) were examined in alert cats during vertical vestibulo-ocular reflex induced by sinusoidal rotation (at 0.11 Hz±10 deg, or 0.31 Hz±5 deg) in a variety of vertical planes using a null point analysis. The results were compared with the angles of anatomical and functional planes of vertical canals reported by Blanks et al. (1972) and Robinson (1982), and with the angles of vertical eye muscles measured in this study and by Ezure and Graf (1984). 2. Maximal activation directions of 23 cells (21 burst-tonic and 2 tonic neurons) were determined from their responses during rotation in 4 or more different vertical planes. All cells showed sinusoidal gain curves and virtually constant phase values except near the null regions, suggesting that their responses were evoked primarily by canal inputs. Phase values of 5 cells near the null regions depended on the rotation plane, suggesting additional otolith inputs. We used a measurement error range of ±10 deg for calculating the maximal activation directions from the null regions of individual cells and the values of error ranges of null calculation. Of the 23, the maximal activation directions of 7 cells were outside the measurement error ranges of vertical eye muscle angles and within the ranges of vertical canal angles (class A), those of 5 cells were within the ranges of eye muscle angles and outside the ranges of vertical canal angles (class B), and those of the remaining 11 cells were in the overlapping ranges for both angles (class C). Even if only the cells in which 5 or more measurement points were taken to determine maximal activation directions (n = 15), the results were similar. During vertical rotation with the head orientation +60 deg off the pitch plane, dissociation of cell activity and vertical compensatory eye movement was observed in 5 cells in class A or C that had null angles near +45 deg. These results suggest that the cells in class A and B carried individual vertical canal and oculomotor signals, respectively, although it is difficult to tell for the majority of cells (class C) which signals they reflected. Some cells in class A and C were antidromically activated from the medial longitudinal fasciculus at the level of abducens nucleus, suggesting that the signals carried by these cells may be sent to the lower brainstem. 3. Most burst-tonic neurons did not respond to horizontal rotation; significant responses were obtained in only 3 of 10 cells tested for which the gain was only 14–17% of their maximal vertical gain. There was no clear difference in gain or phase values of the responses to vertical rotation, or in eye position sensitivity (during spontaneous saccades) between cells whose responses coincided with individual vertical canal angles and those matching the angles of vertical recti muscles. The values of phase lag (re head acceleration during pitch rotation) and eye position sensitivity of these cells are still smaller compared to those of extraocular motoneurons reported by Delgado-Garcia et al. (1986), although they were larger than those of secondary vestibulo-ocular neurons (Perlmutter et al. 1988). All these results suggest that the signals carried by burst-tonic and tonic neurons in the INC region are different from oculomotor signals. 4. Similar analysis was done for comparison for 19 other cells that did not show close correlation with spontaneous eye movement but whose activity was clearly modulated by pitch rotation (pitch cells). More than a half (10/19) had maximal activation directions outside the measurement error ranges of individual vertical canal angles, and many shifted towards roll. Horizontal rotation produced responses with higher gain than burst-tonic neurons, suggesting a difference in the spatial response properties of burst-tonic and tonic neurons on one hand and pitch cells on the other.

Notes: Summary (1) Discharge characteristics of neurons in the region of the interstitial nucleus of Cajal (INC) were studied in alert cats during spontaneous or visually induced eye movement and sinusoidal vertical (pitch) rotation. Activity of a majority of cells (n = 68) was closely related to vertical eye position with or without bursting activity during on-direction saccades. They were called vertical burst-tonic (n = 62) and tonic (n = 6) neurons. Mean discharge rates for individual cells when the eye was near the primary position ranged from 35 to 133 (mean 75) spikes/s with a coefficient of variation (CV) ranging from 0.04 to 0.29 (mean 0.15). Average rate position curves were linear for the great majority of these cells with a mean slope of 3.9 ± 1.2 SD spikes/s/deg. (2) The burst index was defined as the difference in discharge rate between maximal rate during an on-direction saccade and the tonic rate after the saccade. The values of mean burst index for individual cells ranged from 8 to 352 (mean 135) spikes/s. Tonic neurons had a burst index lower than 60 spikes/s and were distributed in the lower end of the continuous histogram, suggesting that burst-tonic and tonic neurons may be a continuous group with varying degrees of burst components. During off-direction saccades, a pause was not always observed, although discharge rate consistently decreased and pauses were seen when saccades were made further in the off-direction toward recruitment thresholds. Significant positive correlation was observed between average discharge rate during off- as well as on-direction saccades and tonic discharge rate after saccades for individual cells, which was not due to cats making saccades mainly from the primary position. (3) During pitch rotation at 0.11 Hz (±10 deg), burst-tonic and tonic neurons had mean phase lag and gain of 128 (±13 SD) deg and 4.2 (±1.7 SD) spikes/s/deg/s2 relative to head acceleration. During pitch rotation of a wide frequency range (0.044–0.495 Hz), the values of phase lag were mostly constant (120–140 deg), while simultaneously recorded vertical VOR showed the mean phase lag of 178 deg. Vertical eye position sensitivity and pitch gain (re head position) showed significant positive correlation. (4) Comparison of the discharge characteristics of vertical burst-tonic and tonic neurons with those of secondary vestibulo-ocular neurons (Perlmutter et al. 1988) and extraocular motoneurons (Delgado-Garcia et al. 1986) in alert cats suggests that signals carried by burst-tonic and tonic neurons are partially processed signals in vertical VOR and saccades, and different from oculomotor signals. (5) The INC region also contained many cells that did not belong to the above groups but whose activity was clearly modulated by pitch rotation (called pitch cells for the present study, n = 44). Many (n = 23) showed some correlation with vestibular quick phases, and some (n = 12) with visually elicited eye movement, although they showed significantly lower and more irregular discharge rates than burst-tonic and tonic neurons (mean discharge rate when the eye was near the primary position 34, range 3–91, spikes/s; mean CV 0.61, range 0.15–1.7). During pitch rotation they showed the mean phase lag and gain of 119(±26 SD) deg and 3.2(±2.1 SD) spikes/s/deg/s2. Some cells showed a much lower phase lag of about 90 deg. (6) More than half the burst-tonic, tonic and pitch cells tested were antidromically activated by stimuli applied to the ponto-medullary medial longitudinal fasciculus at the level of abducens nucleus, while none of them were activated from the inferior olive, suggesting that vertical eye position signals carried by some burst-tonic and tonic neurons are carried to the lower brainstem.

Notes: Summary 1. A total of 43 neurons that showed a close correlation with vertical eye movement with a burst-tonic or tonic type response during spontaneous saccades, were recorded within, and in the close vicinity of, the interstitial nucleus of Cajal (INC) in alert cats. Neuronal responses to sinusoidal vertical linear acceleration (0.2–0.85 Hz, amplitude 10.5 cm) and optokinetic stimuli (0.1–1.0 Hz, amplitude 10.5 cm), were examined. 2. All 43 eye movement-related neurons responded to sinusoidal vertical linear acceleration in the presence of a stationary visual pattern in correlation to robust eye movement responses with compensatory phase. Phase and gain values (re stimulus position) of response of individual cells were independent of the stimulus frequencies tested. Of these, 33 cells were examined during linear acceleration without visual input. Most cells (27/33) did not respond even when a weak linear vestibulo-ocular reflex was present (6/27). The remaining 6 cells (6/33) responded to linear acceleration. Their mean phase values advanced by 80 ° and gain dropped by 55% compared to the responses with visual inputs. 3. Twenty eight of the 43 cells were examined during vertical optokinetic stimuli. The activity of all 28 cells was modulated in correlation to eye movement responses. Response phase showed more lag, and gain decreased as stimulus frequencies increased, similar to optokinetic eye movement responses. 4. The close correlation between the activity of eye movement-related neurons in the INC region and robust eye movements during linear acceleration with visual inputs and optokinetic stimuli suggest that these neurons are involved in some aspect of vertical eye position generation during such stimuli.

Notes: Summary 1. Experiments were performed in cats to determine whether the head tilt following a unilateral lesion of the interstitial nucleus of Cajal (INC) can be attributed to removal of interstitiospihal fibers which have direct excitatory synaptic connections with ipsilateral neck extensor (biventer cervicis-complexus) and flexor (sternocleidomastoid, SCM) motoneurons. Unilateral INC lesions were made either electrolytically or reversibly by procaine infusion into the INC, and electromyographic activity was recorded bilaterally from biventer (BIV), splenius (SP) and SCM muscles. In both groups of lesions, activity of the ipsilateral SP and BIV was higher than that of the contralateral ones. When procaine was infused into the INC of awake cats, an increase of activity of the ipsilateral SP began before the cats presented the typical head tilt to the opposite side. Bilateral INC lesions caused dorsiflexion of the head. These results indicate that the head tilt resulting from unilateral INC lesions can not be explained by simple removal of the ipsilateral, direct excitatory interstitioneck impulses. 2. When unilateral INC lesions were combined with hemilabyrinthectomies, cats that were given labyrinthectomies on the side opposite to the previous INC lesions showed very severe head tilt, whereas cats that received labyrinthectomies on the same side did not show obvious head tilt. Furthermore, it took a much longer time for the cats of the former group to compensate the head tilt than it took those that had single lesions of the INC or labyrinth. These results suggest that the INC and labyrinth interact in the control of head posture and that the INC also plays a role in vestibular compensation. However, when bilatral INC lesions were combined with hemilabyrinthectomies, cats that had previously received bilateral INC lesions and which had fully compensated the head posture recuperated from vestibular symptoms following hemilabyrinthectomy within one to two weeks. Moreover, bilateral INC lesions that were performed in cats which had previously been given hemilabyrinthectomies and in which vestibular symptoms were well compensated did not produce any recurrence of vestibular symptoms. These results indicate that although the INC plays a role in the control of head posture following hemilabyrinthectomy, it is not needed for coarse vestibular compensation.

Notes: Summary (1) Spikes of neurons in the medial and descending vestibular nuclei were recorded extracellularly and their responses to stimulation of the interstitial nucleus of Cajal (INC) were studied in cerebellectomized cats under chloralose anesthesia. Stimuli applied in the ipsilateral INC excited 37% of neurons that did not exhibit spontaneous activity. About 84% of spontaneously discharging neurons were influenced by the INC; typical responses were excitation (35%), inhibition (22%) and excitation followed by inhibition (27%). Of the neurons that were excited, 24% fired monosynaptically. Such monosynaptic activation was evoked by stimulating the INC and midbrain medial longitudinal fasciculus (MLF), but was not evoked by stimulating the lateral midbrain reticular formation. Polysynaptic excitation or inhibition was evoked more widely, but the lowest threshold points were within the INC. Stimulation of the contralateral INC also evoked polysynaptic excitation or inhibition. However, the frequency of occurrence of the evoked responses was significantly smaller compared to the ipsilateral responses. (2) Intracellular recordings revealed that some medial and lateral vestibular neurons received monosynaptic excitatory postsynaptic potentials (EPSPs), others received polysynaptic EPSPs or inhibitory postsynaptic potentials (IPSPs) from the ipsilateral INC. The minimum latency for the IPSPs suggests that the pathway is at least disynaptic. No significant collision was observed between monosynaptic EPSPs evoked by the ipsilateral INC and contralateral vestibular nuclei. Acute lesions that damaged the pontine MLF and part of the reticular formation did not abolish monosynaptic responses of vestibular neurons by the INC. Depth threshold curves for mono- or polysynaptic responses drawn before and after the lesions were virtually similar. Antidromic thresholds of interstitio-vestibular fibers evoked from the pontine MLF showed that a great majority of these fibers run outside the MLF at the pontine level. These results control for vestibular axon reflexes, since vestibulo-interstitial fibers ascend within the MLF (cf. Gacek 1971). (3) Responses to stimulation of the INC were not different among different types of canal responding neurons; vertical and horizontal canal responding neurons received similar effects. However, canal responding neurons that received excitation from the contralateral vestibular nerve were activated more frequently by the INC than those that received inhibition (χ2 test, p〈0.01). Qualitatively similar results were obtained from vestibular neurons that had different projection sites; vestibulospinal, contralateral INC-projecting and contralateral vestibular nuclei-projecting neurons received similar effects. (4) Vestibulo-collic reflexes, studied with EMG, were modified by preceding INC stimulation. Intracellular recordings from some neck motoneurons showed that disynaptic EPSPs evoked by stimulation of the contralateral vestibular nerve were modified by preceding INC stimulation applied ipsilateral to the stimulated vestibular nerve. INC stimulation alone did not evoke any response in these motoneurons, suggesting that the interaction of the labyrinthine and interstitial effects occurred at least in part at the vestibular nuclei. (5) Some medial and descending vestibular neurons showed multiple branching, projecting to the contralateral INC, C1 or contralateral vestibular nuclei. About 34% of neurons that projected to the contralateral INC were also antidromically activated from the C1; some of them received vertical canal inputs.

Notes: Summary Interstitiospinal neurons were activated by antidromic stimulation of the spinal cord ventromedial funiculus at C1 and C4 in cerebellectomized cats under chlor alose anesthesia. Neurons responding only to C1 were classified as N cells and those responding both to C1 and C4 were classified as D cells, as in previous experiments (Fukushima et al. 1980a). Vestibular branching interstitiospinal and reticulospinal neurons were also identified as in the previous experiments. Stimulation of the ipsilateral pericruciate cortex evoked firing in 31% of N cells, 41% of D cells and 35% of vestibular branching neurons, while stimulation of the contralateral cortex excited 6% of N cells, 29% of D cells and 14% of vestibular branching neurons. Response latencies ranged from 2 to 15 ms after the effective pulse. By measuring the thresholds of activation of these neurons while changing the depth of the stimulating electrodes, and by mapping the cortical areas, it was shown that the lowest threshold areas were in the frontal eye fields and the anterior sigmoid gyrus near the presylvian sulcus (Area 6). Stimulation of the latter area often evoked neck or shoulder muscle contraction. Stimulation in the deep layers of the ipsilateral superior colliculus evoked firing in about 20% of interstitiospinal neurons and about 42% of vestibular branching neurons, with typical latencies 2–3 ms after the effective pulse, while stimulation of the contralateral superior colliculus was rarely effective. N cells and D cells responded similarly. Thresholds for activation were high in the intermediate tectal layers and declined as the electrodes entered the underlying tegmentum. This suggests that the superior colliculus is not the main source of synaptic inputs to these neurons. Low threshold points were found above the deep fiber layer when stimulating electrodes were inserted into the pretectum. Stimulation of the C2 biventer cervicis nerve excited about 8% of N cells, 18% of D cells, and 15% of vestibular branching neurons bilaterally with typical latencies around 10 ms. Similar results were obtained when C2 splenius nerves were stimulated. The fibers responsible for such excitation are probably group II, since stimuli stronger than 1.8 times threshold of the lowest threshold fibers were needed to evoke excitation. Response decrement was often observed when stimuli were repeated at 1/s, while no such decrement was observed at the rate of 1/3 s. When the convergence of cortical and labyrinthine excitatory inputs was studied, 36% of interstitiospinal neurons received single inputs either from the pericruciate cortex or from the labyrinth, 22% of neurons received convergent excitation from both and the remaining 42% did not respond to either stimulus. Although vestibular branching neurons rarely received labyrinthine inputs, they frequently showed convergence of excitation to stimulation of the frontal cortex, superior colliculus and vestibular nuclei.