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Notes: Abstract The influence of neointima formation on functional characteristics was investigated in rat carotid artery preparations. The process of intimal hyperplasia development in the injured carotid arteries was followed in time both morphologically and morphometrically. Simultaneously with the loss of endothelial cells due to the balloon injury procedure, the vasodilator responses to methacholine were abolished. The sensitivity for the α1-adrenoceptor agonist phenylephrine appeared to be increased only immediately after injury. The balloon injury method led to significant neointima formation in the rat left common carotid artery 14 days after the intervention. Eight weeks after balloon injury, the neointimal mass reached its maximum. Parallel to the development of intimal hyperplasia, the α1-mediated vasoconstrictor responses to phenylephrine were significantly impaired. After 12 weeks of observation, reoccurrence of mature endothelial cells on the luminal surface of the neointima could be observed. Simultaneously, the vascular responses to phenylephrine and methacholine recovered. The vasoconstrictor responses to high potassium concentrations (100 mM) as well as the vasodilator effects of sodium nitroprusside appeared to be uninfluenced by balloon injury throughout the period of observation. From this study we conclude that both the receptor-mediated contractile responses to α1-adrenoceptor stimulation and the endothelium-dependent vasodilator responses to methacholine become severely impaired as a consequence of balloon catheter injury followed by intimal hyperplasia. However, these pharmacological responses may fully recover upon a prolonged period of endothelial regeneration.

Notes: Abstract The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%±35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10–9 to 5×10–6M) completely inhibited this increase, with an IC50 value of 3.02±1.08×10–7M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1±0.8μM. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicityin vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the Bmax to 1341±192fmol mg–1. When U-83836E was coadministered with KA, the Bmax was reduced to 765±122fmol mg–1, which was not significantly different from the Bmax obtained from untreated rats (Bmax: 518±33fmol mg–1). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.

Notes: Abstract Glucagon-like peptide-1 binding sites have been reported in peripheral tissues including muscle. However, the potential extra-pancreatic effects of glucagon-like peptide-1(7-36)amide are controversial. To evaluate whether glucagon-like peptide-1(7-36)amide has any effects on skeletal muscle glucose transport, isolated rat soleus muscles were incubated in increasing concentrations of insulin (0–150 nmol/l) in the presence or absence of 1 nmol/l glucagon-like peptide-1(7-36)amide for 3 h. Subsequently glucose transport was measured as uptake of [3H]-O-methylglucose. It was found that glucagon-like peptide-(7-36)amide has a small but significant stimulating effect on skeletal muscle glucose transport independent of the insulin concentration (P〈0.01). However, because of the magnitude of the observed effect, the physiological importance of glucagon-like peptide-1 (7-36)amide on skeletal muscle glucose metabolism is questionable.

Notes: Abstract  A novel immunization protocol together with stringent selection criteria have been employed to generate a new murine monoclonal antibody (’’D8’’, isotype IgG1, kappa) which specifically recognizes the human p170 drug resistance glycoprotein. This antibody is directed towards a defined peptide sequence located in the −COOH terminal region of the first external loop of the molecule. It is reactive with its epitope within the intact native glycoprotein in formalin-fixed and conventionally processed histological tissues, in flow-cytometric preparations and by Western blotting. The antibody precipitates its target peptide sequence from solution, and thus may be a useful reagent with which to establish an ELISA, RIMA or other similar assay. The peptide epitope recognized by this monoclonal antibody is restricted to the human MDR1 gene product and is not contained within the rodent homologue of the P-170 molecule. Immunohistochemistry has consistently failed to detect this epitope in rodent tissues, thus confirming that it does not exhibit the cross-reactivity of other currently available anti-P-glycoprotein monoclonal antibodies. The experience of this study emphasizes the value of the tuberculin-PPD (purified protein derivative) immunization protocol as a powerful strategy when generating monoclonal antibodies to small synthetic peptides. The resulting monoclonal antibody (D8) will be an invaluable reagent with which to analyse P-170 glycoprotein expression when assessing the role of multidrug resistance in human cancers.

Notes: Abstract In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1–2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.

Notes: Abstract Tacrolimus (FK506) is an effective and relatively safe novel immunosuppressant able to revert refractory rejection after pediatric liver transplantation (LTx). Between April 1993 and October 1996, 20 pediatric patients were converted to tacrolimus for biopsy-proven, steroid-resistant liver rejection. The mean follow-up was 18 months. The median time from LTx to switch was 20 days. Tacrolimus was administered per os at a mean dosage of 0.23 mg/kg per day to maintain median blood levels of 10.8 ng/ml at 1 week and 9.2 ng/ml at 1 year from the switch. Of the 20 patients, 15 are alive and they all recovered from rejection without the need of OKT3 after conversion. The major causes of death were: one multiorgan failure, two infections (cytomegalovirus Aspergillus), one bowel perforation, and one posttransplant lymphoproliferative disease. One patient experienced late side effects and was reconverted to cyclosporine when she was already rescued from hepatic allograft rejection. The results confirm that an earlier conversion to tacrolimus should be recommended after pediatric liver transplantation in order to revert hepatic allograft rejection with the best safety profile.

Notes: Abstract. Hypercalciuria was induced in female Sprague-Dawley rats, aged 40±2 days, by 7-day administration (mean±SEM) of calcitriol (5.4±0.1 ng/100 g per day, intraperitoneal), furosemide (14.9±1.9 mg/100 g per day, oral), or ammonium chloride (3.8±0.1 mEq/100 g per day, oral). Calciuria increased from 1.9±0.2, 1.6±0.2, and 1.9±0.3 to 5.4±0.5, 4.0±0.9, and 5.4±0.5 mg/100 g per day in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC, n = 10) groups, respectively. Calciuria did not change (1.9±0.3 vs. 1.6±0.1 mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats became hypercalciuric as assessed by urine calcium excretion above the 90th percentile of normal values. Hypercalciuria was of similar degree in the three groups of rats and was not associated with hypercalcemia, metabolic acidosis, severe serum electrolyte imbalance, or growth impairment. VD rats had low serum parathyroid hormone (PTH) concentrations (3.0±0.5 pg/ml vs. 15.8±1.3 pg/ml in controls, P 〈0.05), whereas serum PTH was not significantly elevated in F rats (16.2±1.8 pg/ml). Thus, the protocol caused three forms of hypercalciuria that mimicked the clinical conditions of idiopathic hypercalciuria in humans and may clearly be differentiated according to their mechanism of production. This experimental model of normocalcemic hypercalciuria may be useful to clarify unknown aspects of pathogenesis and pathophysiology of idiopathic hypercalciuria in children.

Notes: Abstract In d-amphetamine-treated (4.0 mg kg–1 s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5–20.0 µg kg–1 s.c.) and raclopride (12.5–100.0 µg kg–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5 m2). Thus, at the low doses of SCH-23390 (2.5–10.0 µg kg–1) or raclopride (12.5–50.0 µg kg–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 µg kg–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 µg kg–1) and the corresponding raclopride-induced (12.5 µg kg–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 µg kg–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the α1-adrenoceptor antagonist prazosin (1.0 mg kg–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D1 and D2/3 receptors.

Notes: Abstract The influence of pregnancy on the role of nitric oxide (NO) in gastric emptying and in non-adrenergic non-cholinergic (NANC) relaxation was studied in rats. The gastric emptying of a non-nutrient liquid solution and of polysterene beads was studied in non-pregnant (NP), 6 to 7 days pregnant (P7) and 18 to 20 days pregnant (P20) rats. Longitudinal muscle strips of the gastric fundus and circular muscle strips of the pylorus were isolated from NP and P20 rats and NANC relaxations were induced by electrical field stimulation. The gastric emptying of the liquid meal was significantly increased in P20 rats as compared to NP and P7 rats. In NP rats, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently (50–150 mg/kg ip) reduced the gastric liquid emptying; the inhibitory effect of 100 mg/kg L-NAME ip was prevented by 400 mg/kg ip L-arginine and was mimicked by 100 mg/kg NG-monomethyl-L-arginine (L-NMMA). The percentage inhibition of the liquid emptying by L-NAME did not differ between the 3 groups, except for the dose of 150 mg/kg ip where it was significantly lower in P20 rats. The gastric emptying of beads was 54% in NP, 36% in P7 and 69% in P20 rats but these values were not significantly different illustrating the great variability. The inhibitory effect of L-NAME (25 and 100 mg/kg ip) on the emptying of beads did not differ between the 3 groups. As evaluated in NP rats, the inhibitory effect of L-NAME on the gastric emptying of the beads was not prevented by L-arginine nor mimicked by L–NMMA. Electrical field stimulation in NANC conditions induced frequency-dependent relaxations in the fundus strips and relaxations followed by rebound contractions in the pyloric strips. These electrically induced NANC relaxations and their reduction by 3×10–4 M L-NAME were not different between NP and P20 rats. It can be concluded that no evidence for a regulatory role of NO in the gastric emptying of the beads was found, and that the nitrergic contribution to the gastric emptying of liquids and to the fundic and pyloric NANC relaxations was not influenced by pregnancy in rats.

Notes: Abstract The aim of the present study was to evaluate the effect of oxytocin on survival of musculocutaneous flaps in male Sprague-Dawley rats. For this purpose oxytocin (0.1 or 1.0 mg/kg), an oxytocin antagonist (1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin) (1.0 mg/kg) alone or in combination with oxytocin (1.0 mg/kg) or saline was given subcutaneously (s.c.), 24 hours and 1 hour before and 24 hours after flap surgery. In addition, oxytocin (1 µg/kg) or saline was given intracerebroventricularly (i.c.v.) according to the same schedule. Six days after surgery the amount of viable tissue was measured. Oxytocin 1.0 (but not 0.1) mg/kg s.c. and 1.0 µg/kg i.c.v. increased survival of the flaps (s.c.: 13.8±14.6% versus 6.10±5.45%; p〈0.05 and i.c.v.: 25.5±14.0% versus 10.3±5.79%; p〈0.01). This effect was abolished by the oxytocin antagonist. Furthermore, the oxytocin-treated rats had significantly higher plasma levels of insulin-like growth factor-1 (IGF-1) (p〈0.05). These data indicate that oxytocin increases the survival of musculocutaneous flaps. The effect seems to be exerted within the central nervous system since a 1000 fold lower dose of oxytocin given i.c.v. increased flap survival to the same extent as the s.c. given dose. IGF-1 might be one of the mediators of this effect.

Notes: Abstract  Some alleles of the major histocompatibility complex (MHC) genes have a reticulate pattern of evolution, probably resulting from the exchange of segments by gene conversion or recombination. Here we compare the extent and patterns of reticulate evolution among the classical class I and class II loci of the human MHC using the recently developed compatibility and partition matrix methods. A complex pattern is revealed with substantial differences among loci in the extent and pattern of reticulation. Extremely high levels of reticulation are observed at HLA-B and HLA-DPB1, high levels at HLA-A and HLA-DRB1, moderate levels at HLA-C and HLA-DQB1, and low levels at HLA-DQA1. The reticulate events are concentrated in the exons encoding the highly variable, peptide-binding domains, suggesting that the sequence combinations produced by these events are maintained by natural selection.

Notes: Abstract Purpose: To identify and characterize the specificity and potency of topoisomerase II-interacting antitumour drugs in an in vivo model utilizing the yeast Saccharomyces cerevisiae. Methods: Four yeast transformants were selected for the expression of either human or yeast DNA topoisomerase II at different, biologically relevant, levels under the tight control of promoters of various strengths. Results: Analyses of 24 drugs permitted their classification into three distinct groups, depending on whether they induced topoisomerase II-related cytotoxicity (etoposide), showed nonspecific cytotoxicity (camptothecin), or exerted no cytotoxicity at all (vinorelbine). Within the first group different patterns of action were distinguishable: (1) classical topoisomerase II expression-dependent cytotoxicity for both species of enzyme (e.g. etoposide, amsacrine, doxorubicin, actinomycin D), although amsacrine and TOP 53 were more active, respectively, on human and yeast topoisomerase II; and (2) compounds that appeared to poison only one species of topoisomerase II with, for example, genistein and the bisdioxopiperazine ICRF-193 lethally targeting only the human type, and mitoxantrone only the yeast isozyme. Three of the 16 known topoisomerase II inhibitors tested were not correctly identified with this assay, possibly owing to restricted cell wall permeability or to the absence of correct processing pathways such as, for example, in the case of the prodrug etopophos. Conclusion: This methodology, in vivo in yeast, selected for a large range of potent topoisomerase II-targeting anticancer agents. Of particular interest in this yeast model, and in contrast to yeast topoisomerase II, human topoisomerase II was shown to confer dominant sensitivity in the presence of the series of bisdioxopiperazine derivatives tested. This assay therefore has the potential easily to identify and characterize the potency and specificity of synthesized anticancer drugs with modified original chemical structures or those present, for example, in natural plant extracts or marine organisms.

Notes: Abstract A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from peripheral blood lymphocytes of patients with multifocal motor neuropathy and Guillain-Barré syndrome. In solid-phase immunoassay, the antibodies react with GM1, and also in differing degrees to the structurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM1 antibodies to epitopes within the human nervous system. Antibodies were observed to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots, dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites conventionally regarded as pathologically affected in anti-GM1 antibody-associated motor nerve syndromes. This undermines a model of disease pathogenesis based solely on antigen distribution. Factors other than the presence or absence of antigen, such as the local ganglioside topography, antibody penetration into, and pathophysiological vulnerability of a particular site may also influence the clinicopathological outcome of anti-GM1 antibody-mediated autoimmune attack.

Notes: Abstract Insulin-dependent diabetes mellitus is a chronic metabolic disease that causes long-term secondary complications such as neuropathy. The occurrence of diabetic neuropathy has generally been thought of as being associated with hyperglycaemia. However, in a previous light microscopic examination of plantar nerves in diabetic BB/Wor rats treated with insulin implants we found that eu-/hyperglycaemic rats present a normal picture, whereas eu-/hypoglycaemic rats show severe changes. The aim of the present work is to supplement our previous light microscopic report with electron microsocpic data from the lateral plantar nerve of normal, eu-/hyperglycaemic and eu-/hypoglycaemic BB/Wor rats. Under the electron microscope lateral plantar nerves collected from eu-/hyperglycaemic rats presented a qualitatively normal picture. In addition, the fibre numbers and the size distribution of the myelinated fibres were normal. In contrast, specimens from eu-/hypoglycaemic BB/Wor rats showed severe qualitative changes, interpreted as signs of axonal de- and regeneration. The total number of axons was somewhat subnormal and the sizes of the myelinated fibres were strongly shifted towards smaller diameters. These data confirm our previous light microscopic observations. We conclude that eu-/hypoglycaemic BB/Wor rats treated with insulin implants, but not similarly treated eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.

Notes: Abstract B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a major role in neurite growth during development and regeneration as well as in synaptic remodelling. In the mature intact central nervous system, intense B-50 immunoreactivity (B-50-IR) can still be detected in regions which maintain residual capacity for structural re-organization. B-50 expression has been studied extensively in laboratory animals; however, its distribution and regulation in the human spinal cord is largely unknown. As a first step to analyze lesion-induced structural alterations, we investigated the distribution of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal horn at all segmental levels, the intermediolateral nucleus at thoracic levels and Onuf’s nucleus at sacral levels. Scattered neurons, particularly in the ventral horn of lumbar and sacral segmental levels (and occasionally also in Clarke’s nucleus) displayed intense B-50-IR in close apposition to the perikaryal and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated that B-50 mRNA could also be detected in neurons of the ventral horn and also in the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the normal human spinal cord shows a marked similarity to that reported in experimental animals, including the selective labelling of Onuf’s nucleus. However, the strong B-50-IR on the surface of some large anterior horn motor neurons has not been observed in other mammals. This finding might reflect a particular state of readiness for synaptic plasticity.

Notes: Abstract Following focal cerebral ischemia, neuronal cell death is detected in remote areas of the brain, including the ipsilateral thalamus and substantia nigra (SN), as well as in the ischemic core. We have investigated protein synthesis in the remote areas of rats exposed to focal ischemia using autoradiography. The proximal portion of the left middle cerebral artery (MCA) was permanently occluded, and at various periods (6 h, 2, 4 and 7 days and 2 and 4 weeks following ischemia) animals received a single dose of l-[2,3-3H]valine (6.7 mCi/kg). Brain sections containing the thalamus and SN were processed for autoradiography. In the ipsilateral cerebral cortex and striatum, marked impairment of protein synthesis was observed and was never completely recovered during the experiment. No changes in protein synthesis in the ipsilateral thalamus were detected during the experiment. However, a change in protein synthesis was demonstrated in the ipsilateral SN. At 2 days after MCA occlusion, incorporation of [3H]valine into the whole zona reticulata of the ipsilateral SN was slightly enhanced and the increase became evident at 4 days after ischemia. Increased incorporation of [3H]valine began to be localized in the lateral portion of the zona reticulata after 7 days and continued up to 4 weeks following ischemia. Enhanced protein synthesis during the early stage (2 and 4 days after ischemia) may be due to the activated function of the neurons in the zona reticulata and that during the late stage (7 days and 2 and 4 weeks) after ischemia to astroglial proliferation

Notes: Abstract  The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.

Notes: Abstract Hyperthermia has been shown to inhibit glioma growth both in vitro and in vivo, and has been reported to induce apoptosis of a variety of cells. We investigated the role of apoptosis in tumor cell death following hyperthermia in a rat glioma model representing human glioblastoma. Apoptotic cell death was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and hematoxylin and eosin (H & E) staining. We also examined c-Jun expression immunohistochemically. Apoptotic cell death in rat brain tumors that grew after implantation of C6 glioma cells showed regional differences. In all rats, apoptotic cells, characterized by extreme chromatin condensation and fragmented nuclei with apoptotic bodies in H & E-stained sections, were observed in the gliomas’ necrotic cores. TUNEL-positive cells were observed in the border zones between necrotic and vital tumor cells. Before hyperthermia, TUNEL-positive cells were sporadically distributed in the vital tumor tissue. After hyperthermia, the number of TUNEL-positive cells in the peripheral region of the tumor mass increased significantly, reached a peak after 6 h and returned to the basal level within 24 h (P 〈 0.01). C-Jun protein immunoreactivity was not observed in the cells at the tumor periphery. These data indicate that significantly apoptotic cell death unrelated to c-Jun expression occurs after hyperthermia, and that this form of cell death may be the mechanism of tumor regression following hyperthermia treatment of intracranial gliomas.

Notes: Abstract  A number of previous studies have indicated that lectin histochemistry is an obvious choice for characterizing the vomeronasal system. However, apparently inconsistent results have been obtained: notably, the affinity with which various lectins bind to the accessory olfactory bulb varies among taxa, even considering closely related species. In the present study, the binding patterns of seven lectins in the rat accessory olfactory bulb, vomeronasal nerves and vomeronasal duct were investigated. The Bandeiraea simplicifolia lectin bound exclusively to the vomeronasal nerve and glomerular layers of the accessory olfactory bulb, while the Ulex europeus and Lycopersicon esculentum lectins bound to these regions and additionally to the nerve and glomerular layers of the main olfactory bulb. Soybean agglutinin showed a similar pattern to that obtained with the Ulex europeus and Lycopersicon esculentum lectins, though it also faintly labelled other parts of the structures examined. The Vicia villosa and Erythrina cristagalli lectins were not specific for the vomeronasal system, since they labelled grey and white matters in structures including the lateral olfactory tract and the anterior olfactory nuclei. The Dolichos biflorus lectin did not bind to vomeronasal tissues. The observed patterns of binding in the accessory olfactory bulb were consistent with those observed in the vomeronasal nerves, but unlike those observed in the epithelium of the vomeronasal duct. This latter result probably reflects binding of lectins to sugar residues contained in secreted mucus rather than those in epithelial nerve endings.

Notes: Abstract  Pituitary adenylate cyclase-activating peptide (PACAP)-immunoreactive (IR) neurons in the myenteric and submucosal plexus of the rat small and large intestine were examined by immunostaining with purified polyclonal antiserum against PACAP (1–15), using both light and electron microscopy. Many PACAP-IR neuronal cell bodies and fibers were found in the myenteric and submucosal plexus. Many of the PACAP-IR fibers originated from the cell bodies of the myenteric and submucosal ganglia. The ganglia were also innervated by PACAP-IR fibers. PACAP-IR fibers penetrated both the circular and longitudinal muscle layers, confirming the previous observations indicating that PACAP neurons act as motor neurons. Ultrastructural study demonstrated that PACAP-IR nerve terminals formed synaptic contacts with PACAP-IR nerve cell bodies or dendritic processes. This observation suggests that PACAP-IR neurons innervate other PACAP-IR neurons, and that PACAP neurons work as interneurons in the enteric nervous system. PACAP-IR nerve cells received not only PACAP-positive nerve terminal input also PACAP-negative nerve terminal input. It also suggests that PACAP neurons are regulated not only by PACAP-IR enteric neurons, but also by neurons originating elsewhere. Our observations support the view that PACAP-IR neurons are involved in the control of gut motility.

Notes: Abstract  It is unknown whether cells in the midportion of Meckel’s cartilage undergo transformation into other kinds of cell or whether resorption of cells occurs during development. Therefore, the midportion of Meckel’s cartilage from the mouse and the rat was subdivided into anterior and posterior portions. The ultimate fates of these tissues were analyzed with a focus on resorption-related cells, death of chondrocytes by apoptosis, and transformation of the chondrocytes themselves. Cellular and extracellular features of mouse Meckel’s cartilage were observed after von Kossa’s staining and staining for acid phosphatase (APase) activity, as well as by light and electron microscopy. To identify resorbing cells, immunostaining specific for macrophages and staining for tartrate-resistant acid phosphatase (TRAP) were performed. The DNA nick end-labeling (TUNEL) method was used for the detection of death of chondrocytes by apoptosis. The replacement of the extracellular matrix of rat Meckel’s cartilage was examined with double immunofluorescence staining for type I and type II collagens. When the anterior midportion from embryonic mice on day 18 was examined after von Kossa’s staining, it was clear that the extracellular matrix had already calcified and vascularization had been initiated that reflected the calcified matrix. TRAP staining and immunostaining for macrophages revealed two types of osteoclast and macrophages that were involved in resorption of the matrix. In the posterior midportion, no vascular invasion was evident, and chondrocytes were transformed directly into fibroblastic cells by phenotypic conversion. In such cells we found reaction products specific for APase activity, suggestive of the intracellular degradation of fine collagenous fibrils. Double immunofluorescence staining showed that cartilage-specific type II collagen was replaced by type I collagen with the phenotypic transformation to fibroblastic cells. There were no significant changes in the number of TUNEL-positive apoptotic cells from day 17 of gestation to day 6 after parturition. Death of chondrocytes by apoptosis was not, therefore, involved directly in the disappearance of Meckel’s cartilage. These results in the posterior midportion served as an instance of phenotypic switches in differentiated cells from chondrocytes to fibroblast-like cells. The present study indicates that there is a difference between the ultimate fate of cells in the posterior part and that of cells in the anterior part in the midportion of Meckel’s cartilage in the mouse and rat.

Notes: Abstract The endothelial barrier antigen (EBA) recognised by a monoclonal antibody is expressed in rat cerebral microvessels possessing blood-brain barrier properties but only weakly by fenestrated vessels. We have studied the expression of this marker in the spinal cord of control rats and compared the findings with those seen in rats subjected to compression injury at the T8–9 level with a survival period of 4 h, 24 h, 4 days and 9 days. To that end, formalin-fixed paraffin-embedded material was immunostained by the avidin-biotin-peroxidase complex method. Sections from control rats presented a distinct immunostaining at the site of the endothelial cells of almost all microvessels in the grey and white matter of the cord. The anterior and posterior spinal arteries did not show such staining. Neurons and glial cells were unstained. Rats which had survived 4 h after a moderate or severe compression trauma still showed immunoreactivity in intramedullary microvessels at the site of injury. There was a moderate reduction of vascular immunoreactivity at 24 h and a pronounced loss of such reactivity at 4 days after trauma. At 9 days after compression the expression of the endothelial barrier antigen had almost been normalised in the microvessels of the cord. In conclusion, using immunohistochemistry, EBA can be demonstrated in noninjured rat spinal cord microvessels, while the staining disappears at the site of compression trauma to the cord. The EBA marker can be used to indicate sites of vascular injury in spinal cord compression injury. The factors causing the disappearance and restitution of the antigen are unknown.

Notes: Abstract Vasa vasorum are adventitial vessels that play a role in pathogenesis of atherosclerosis, aneurysm, vasculitides, and graft vascular disease. The existence of vasa vasorum in human intracranial arteries is not yet well defined. The specific aims of this study are to determine whether the human intracranial arteries have vasa vasorum, whether their existence is related to the thickness of tunica media as is in systemic vessels, and whether they are acquired in reaction to pathological conditions, such as atherosclerosis and arterial occlusion. Human intracranial internal carotid (i-ICA), vertebral (i-VA), basilar (BA) and middle cerebral arteries (MCA) from adults, children and newborns were examined. Systemic vessels of comparable medial thickness were used as controls. Immunohistochemical staining for Factor VIII and CD 31 was used to identify the endothelial cells. Human intracranial arteries in neonates, children and adults do not have vasa vasorum, although their medial thickness is comparable to their systemic counterparts with vasa vasorum. Only in adults did the proximal intracranial segments of i-ICA and i-VA reveal a few vasa vasorum-like vessels with unusually large diameter. They were more frequently seen in atherosclerosis and thrombotic but again limited to the proximal segments of i-ICA and i-VA. Completely obstructed bilateral carotid arteries in a child with sickle cell disorder revealed a rich adventitial neovascularization in the proximal intracranial part of the vessel. It is not yet known whether obstruction of the distal segments may create similar neovascularizations. Adventitial neovascularizations seen in the proximal i-ICA and i-VA may represent a focal intracranial extension of the vascular pathologies involving the extracranial segments of major cerebral arteries.

Notes: Abstract While it is established that p53 mutation plays a critical role in the carcinogenesis of astrocytic brain tumors, its role remains to be clarified for other types of tumors in the central nervous system (CNS). Using a yeast-based assay which tests the ability of human p53 to activate transcription, we analyzed p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors (3 central neurocytomas and 1 pineocytoma), 12 primitive neuroectodermal tumors, 14 germ cell tumors (7 germinomas, 7 non-germinomatous tumors), 4 craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in immunocompetent patients, and 5 bone tumors of the skull. The only tumors found to contain p53 mutations were 3 malignant lymphomas. The presence of mutations in these cases was confirmed by DNA sequencing. Given the high accuracy and sensitivity of the yeast assay and previous negative results using conventional techniques, this indicates that p53 mutation is a rare event in non-astrocytic CNS tumor types examined here.

Notes: Abstract Muscular changes in male forest machine operators with work-related neck and shoulder myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius myalgia.

Notes: Abstract We undertook a detailed characterization of the cellular responses to acute global cerebral ischemia complicated by hyperglycemia. Anesthetized, physiologically monitored male Wistar rats received 12.5 min of global forebrain ischemia by bilateral common carotid artery occlusions plus hemorrhagic hypotension to 45 mm Hg. Cranial temperature was maintained at normothermic levels. Hyperglycemic animals received dextrose (2.5 ml of a 25% solution, intraperitoneally) prior to ischemia; this doubled the mean plasma glucose concentration to 296 mg/100 ml. At 3 days (n = 10) or 24 h (n = 4) after ischemia, brains were perfusion-fixed and paraffin-embedded for light microscopic histopathology and for the histochemical visualization of activated microglia and the immunocytochemical visualization of glial fibrillary acid protein. Normal-neuron counts in the vulnerable hippocampal CA1 sector of hyperglycemic-ischemic (HI) rats were reduced to one-third the number observed in normoglycemic-ischemic (NI) animals. Ischemic cell counts in the striatum were increased fivefold or more in HI compared to NI rats, and normal small-neuron counts were reduced by two-thirds. The neocortex and striatum of NI rats showed only mild damage, while the majority of HI rats had extensive lesions, and several showed large cortical, striatal or thalamic infarcts. In addition, widespread cortical ischemic neuronal changes were evident in HI animals. No endothelial alterations were present in NI rats. By contrast, HI rats showed prominent peri- and intravascular polymorphonuclear and monocytic accumulation evident at 24 h; frequent white cell thrombi in pial arterioles on day 3; and thickening of vascular endothelium, with foci of parenchymal rarefaction or microinfarction adjacent to occluded vessels. Prominent microglial activation, often along the course of penetrating blood vessels, was common in the striatum and neocortex of HI animals but was much less extensive in the NI group. Activated microglia in HI rats were typically hypertrophic and amoeboid. These results suggest that the detrimental influence of hyperglycemia in ischemia is initially mediated by an action on vascular endothelium, which in turn leads to widespread foci of infarction and neuronal loss.

Notes: Abstract  This study describes the morphological behaviour of spermatogonia following recovery from two doses of busulfan treatment in the rat. Twenty days after the second intraperitoneal injection of busulfan, the testes lost most of their spermatogenic cells and there were fewer dispersed singly surviving spermatogonia. These surviving cells were in close contact with the basal portions of adjacent Sertoli cells and the shrunken basal lamina, and were the source for repopulating the depleted seminiferous epithelium. During the initial stage of repopulation (48 days later), surviving spermatogonia underwent a phase of active proliferation: type A spermatogonia underwent symmetric and asymmetric divisions; type B spermatogonia underwent asynchronous differentiation. At day 96, normal spermatogenesis was fully recovered in many seminiferous tubules, represented by 80% of the rats regaining various degrees of fertility at day 120. These data provide an additional model for the study of self-renewal of stem spermatogonia and suggest that the asymmetric division of type A spermatogonia and their close contact with both the basal lamina and the Sertoli cells may be involved in regulating the number of stem spermatogonia and the delicate process of normal spermatogenesis.

Notes: Abstract  Groups of 15 male rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5.0 or 10.0% dietary fibre (DF) prepared from sugar beet. The highest food consumption was found in the group with 10% DF in the diet. Food efficiency was highest in the control group. Average body weight increased continuously in all groups without significant differences. Enrichment of the diet with the DF preparation did not substantially influence urinary parameters [pH, specific gravity, protein or activities of aspartate aminotransferase (ASAT), alanine aminopeptidase and alkaline phosphatase (AP)]. Haemoglobin concentration and haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular volume as well as total numbers of erythrocytes, thrombocytes and leukocytes counts did not significantly differ between the groups. Lower counts of eosinophils and neutrophils were measured in rats fed DF-enriched diets. Serum parameters (urea-N, protein, glucose, triglycerides and activities of ASAT, alanine aminotransferase, AP and leucine aminopeptidase) did not differ between groups. As the amount of DF preparation in the diet increased, serum cholesterol was reduced in trend. Furthermore, no significant differences were found between the groups with respect to the organ weights of rats. In conclusion, important or critical dose-related differences in the determined parameters were not found. This sub-acute feeding study showed that no toxic effects were related to used doses of DF which was prepared from sugar beet.

Notes: Abstract  Groups of 15 female rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5 or 10% of a dietary fibre (DF) preparation made on a laboratory scale from sugar beet pulp. This preparation had a total DF content of 72.2%. Its major components were 36.7% cellulose, 16.9% pectin, 16.8% hemicelluloses (HC) and 11.0% protein. The DF preparation from sugar beet exhibited a water-binding capacity (WBC) of 8.9 g H2O/g. As the proportion of DF preparation in the diet increased, up to 15.8% total DF, 4.6% cellulose and 1.9% pectin were found in the feeds. The WBC of the diets was estimated to be 1.4–2.9 g H2O/g. At the end of the experiment, 20.3–64.1% total DF, 10.3–38.2% cellulose, 0.2–7.8% pectin, 4.3–9.2% HC pentoses and 4.3–10.3% HC hexoses were determined in caecum contents (ca. 0.6 g dry weight/rat). The following proportions were found in faeces (3rd week; 1.4–1.9 g dry weight/rat): 34.5–56.9% total DF, 19.5–36.1% cellulose, 6.4–8.4% HC pentoses, 7.4–8.3% HC hexoses. The WBC of faeces ranged from 3.7 g H2O/g to 4.9 g H2O/g. About 30–50% of the daily intake of DF appeared in the faeces. Higher amounts of total DF, pectin and HC pentoses were fermented by gastrointestinal microflora as the concentration of DF preparation from sugar beet in the diet increased. In addition, the fermentation of different DF components could be shown by the monosaccharide composition of caecum contents and faeces.

Notes: Abstract Cadaveric osseoligamentous lower cervical spines (C2-C7) are often used in the investigation of spinal biomechanics in vitro. Surprisingly, however, the techniques of harvesting at postmortem and preparation of cadaveric osseoligamentous lower cervical spine for biomechanical testing have not been described in detail. We describe a simple and effective method that can be readily integrated into the routine autopsy procedure. Points on the avoidance of disfiguring the cadaver and damaging the spinal osseoligamentous structures are highlighted.

Notes: Abstract Aim: The aim of the present paper was to compare the pharmacokinetics of metoprolol in homozygous Caucasian volunteers for the wild-type CYP2D6 allele (CYP2D6*1/CYP2D6*1) and heterozygous (CYP2D6*1/CYP2D6*4) Caucasians. Methods: Thirty-six unrelated healthy male Caucasians were screened for two of the most frequently occurring mutant alleles (CYP2D6*3 and CYP2D6*4) using polymerase chain reaction (PCR). Twenty-four volunteers with a genotype suggesting a rapid hydroxylator phenotype were enrolled in a bioequivalence trial and each received in a randomized, cross-over fashion one of the three formulations compared. Each formulation contained 200 mg metoprolol tartrate/(tablet). In each of the three periods of the trial, one of the formulations was administered under fasting conditions in the morning on 4 consecutive days. Blood for quantification of metoprolol was drawn immediately before the last dose and in selected time intervals thereafter. A sensitive and specific high-performance liquid chromatography (HPLC) method with fluorescence detection was applied for the quantification of metoprolol. Pharmacokinetic parameters were determined for each subject and statistically compared in two groups of 16 homozygous (CYP2D6*1/CYP2D6*1) and six heterozygous (CYP2D6*1/CYP2D6*4) volunteers. Results: Significant differences between homozygous and heterozygous individuals were observed for all pharmacokinetic parameters. The AUC in the course of one those interval of 24 h (AUCτ), minium steady-state concentration (Cmin ss) and average steady-state concentration (Cav ss) values for heterozygous individuals were more than twice those of individuals. Significantly higher values for Css max , t1/2, half-value duration (HVD) and mean residence time (MRT) were also observed in heterozygous volunteers. The higher concentrations of metoprolol in heterozygous individuals also had pharmacodynamic consequences, namely, greater heart rate and blood pressure reduction.

Notes: Abstract Many organisms can easily dispose of toxic inorganic arsenic species through gradual methylation of the element and further urinary excretion. In order to clarify the urinary excretion of arsenobetaine observed in a human case of intoxication by arsine, the capacity of highly methylated arsenical synthesis has been investigated in rats acutely exposed during 1 h to increasing concentrations of the same gas [4 to 80 mg AsH3/m3]. Urinary metabolites of arsenic were determined with good agreement in two (Belgian and Italian) laboratories using two different analytical procedures. The sum of inorganic, mono- and dimethylated metabolites of arsenic in urine was shown to be related to the intensity of exposure to arsine. A biphasic relationship was observed: 1 h exposure to 〉60 mg AsH3/m3 led to metabolite excretion which is roughly 10 times higher than for exposure levels below that limit, suggesting the saturation of a binding site reserve and the availability for metabolism of a greater proportion of the As absorbed above this threshold. Arsenobetaine production, if any, could only be detected when its presence in food was excluded; in addition, amounts appeared negligible and could be disregarded as a common arsenic metabolite in rats.

Notes: Abstract Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO2) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO2-2,2′,3′,4′,5,6-hexachlorobiphenyl (3-MeSO2-CB132); 3-MeSO2-2,2′,3′,4′, 5,5′-hexachlorobiphenyl (3-MeSO2-CB141); 3-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (3-MeSO2-CB149) and 4-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (4-MeSO2-CB149). The congeners were major MeSO2-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO2 metabolites (20 μmol/kg once daily for 4 days) reduced serum total thyroxine levels by 22–44% at a much lower dose than phenobarbital (PB; 431 μmol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO2-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO2-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO2-CB132, 3-MeSO2-CB141 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149. Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.

Notes: Abstract Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to␣most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 μmol/kg per day × 5 days, p.o.) showed brain Hg levels as high as 18 μg/g with slight neurological signs 10␣days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7–8 μg Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for 〉2␣weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT.

Notes: Abstract  Three patients with cerebellar limb ataxia and three age-matched controls performed arm-pointing movements towards a visual stimulus during an experimental procedure using a double-step paradigm in a three-dimensional space. Four types of trajectories were defined: P1, single-step pointing movement towards the visual stimulus in the initial position S1; P2, double-step pointing movement towards S1; P3, double-step straight pointing movement towards the second position S2; and P4, double-step pointing movement towards S2 with an initial direction towards S1. We found that the cerebellar patients, as well as the controls, were able to modify their motor programs, but with impaired timing, severe anomalies in the direction and amplitude of the changed movement trajectories and alteration of the precision of the pointing movements.

Notes: Abstract  Young and elderly subjects performed aiming movements to a visual target with a manipulandum to determine whether the elderly reduce their reliance on visual feedback after extended practice. Reliance on visual feedback was assessed by performance on trials in which the cursor displaying arm movement was unpredictably extinguished. Movements were divided into two subcomponents: a primary, ballistic submovement and a secondary, corrective submovement. For both age groups, removal of visual feedback prior to practice resulted in a decrease in the distance covered in the primary submovement, an increase in the distance of the secondary submovement, and a decrease in endpoint accuracy. After extensive practice with the cursor present, the proportion of distance traveled with the primary submovement was again assessed under trial conditions in which the cursor randomly disappeared. Following practice, the young demonstrated that they were capable of extending the primary submovement distance closer to the target. In addition, primary submovement distance was unaffected by the removal of vision following practice. After practice the elderly did not show evidence of lengthening the primary submovement, and submovement distance and endpoint accuracy continued to be altered by the removal of vision. This suggests that, unlike the young, the elderly do not benefit from practice so that they can place a greater proportion of the movement under program control. Thus, on a relative basis, a greater proportion of their overall movement requires corrective adjustments.

Notes: Abstract  Botulinum toxin is sometimes injected into human eye muscles as an alternative to surgery in the correction of strabismus. Within minutes of botulinum injections into ungulate eye muscles, proprioceptive discharge from muscle spindles decreases dramatically. It is only over 7–48 h, however, that surgically treated strabismus patients usually show an altered proprioceptive signal about eye position, presumably from the palisade endings attached to the global multiply innervated fibers. How quickly will botulinum toxin alter proprioceptive registration of eye position in humans? First, to examine the short-term effects, we measured open-loop pointing responses (which requires knowledge of eye position) in six strabismus patients preinjection and then over a 45 min postinjection period, and in six normal controls over the same time period. Second, to examine the long-term effects, 13 strabismus patients were tested preinjection and then daily over the next 3 weeks, and three normal controls over the same time period. We compared their open-loop pointing responses with the injected eye fixating the target to the photographically determined position of the occluded other eye (a measure of where the patient would point if eye position were determined by efference, not proprioception). There were three groups of patients: esotropes with no previous injection, exotropes with no previous injection, and exotropes with previous injection. First, all patients showed significant correction of their tropias. Second, over the short-term, there was no difference in pointing responses found between the patients and the controls (t(18) = –1.427, P = 0.1706). Third, over the long-term, however, the difference between the pointing responses and eye position information was compared among the four groups across four posttests and a significant difference found (F 3,12 = 58.988, P 〈 0.00001). Only in patients with no previous injections was there altered proprioceptive feedback about eye position. Also, injections into the medial rectus induced a significantly greater proprioceptive response than those injected into the lateral rectus. In humans, botulinum toxin alters proprioception from eye muscles only over the long-term. We suggest that the toxin temporarily affects proprioceptive feedback from palisade endings.

Notes: Abstract  Kinematic abnormalities of fast multijoint movements in cerebellar ataxia include abnormally increased curvature of hand trajectories and an increased hand path and are thought to originate from an impairment in generating appropriate levels of muscle torques to support normal coordination between shoulder and elbow joints. Such a mechanism predicts that kinematic abnormalities are pronounced when fast movements are performed and large muscular torques are required. Experimental evidence that systematically explores the effects of increasing movement velocities on movement kinematics in cerebellar multijoint movements is limited and to some extent contradictory. We, therefore, investigated angular and hand kinematics of natural multijoint pointing movements in patients with cerebellar degenerative disorders and healthy controls. Subjects performed self-paced vertical pointing movements with their right arms at three different target velocities. Limb movements were recorded in three-dimensional space using a two-camera infrared tracking system. Differences between patients and healthy subjects were most prominent when the subjects performed fast movements. Peak hand acceleration and deceleration were similar to normals during slow and moderate velocity movements but were smaller for fast movements. While altering movement velocities had little or no effect on the length of the hand path and angular motion of elbow and shoulder joints in normal subjects, the patients exhibited overshooting motions (hypermetria) of the hand and at both joints as movement velocity increased. Hypermetria at one joint always accompanied hypermetria at the neighboring joint. Peak elbow angular deceleration was markedly delayed in patients compared with normals. Other temporal movement variables such as the relative timing of shoulder and elbow joint motion onsets were normal in patients. Kinematic abnormalities of multijoint arm movements in cerebellar ataxia include hypermetria at both the elbow and the shoulder joint and, as a consequence, irregular and enlarged paths of the hand, and they are marked with fast but not with slow movements. Our findings suggest that kinematic movement abnormalities that characterize cerebellar limb ataxia are related to an impairment in scaling movement variables such as joint acceleration and deceleration normally with movement speed. Most likely, increased hand paths and decomposition of movement during slow movements, as described earlier, result from compensatory mechanisms the patients may employ if maximum movement accuracy is required.

Notes: Abstract  The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-d-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15—20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimualtion.

Notes: Abstract  Two experiments were performed in order to study the effects of lesions of the rostral thalamic reticular nucleus (Rt) on two-way active avoidance. Male wistar rats were subjected to either a bilateral electrolytical lesion of the rostral Rt or to control procedures. After recovery, all rats were trained in either a distributed (five training sessions, ten trials each; experiment I) or a massed (a single 30-trials session; experiment II) two-way, active-avoidance task. The level of long-term retention of the task was assessed 10 days later. Lesioned rats showed an overall higher performance than control rats both in experiment I (with lesions affecting the rostral Rt and small portions of some adjacent nuclei) and in experiment II (with lesions almost restricted to the rostral Rt). In contrast, detrimental effects on other tasks have been reported in the literature. Although it cannot be ruled out that those differences might be due to methodological factors, they also might be indicative of an action of rostral Rt lesions on certain mechanisms (either indirectly or directly related to information processing) that could be differentially required depending on the kind of learning task. The latter possibility is discussed in terms of the role played by this nucleus as a modulator of thalamocortical transmission, attentional mechanisms and cortical arousal.

Notes: Abstract  We studied horizontal eye movements evoked by lateral whole body translation in nine patients who underwent vestibular nerve section. Preoperatively, all had preserved caloric function on both sides. Testing was performed before, 1 week and 6–10 weeks after surgery. Patients were seated upright in an electrically powered car running on a linear track. The car executed acceleration steps of 0.24 g, randomly to the left and right in the dark. The normal response consisted of a bidirectionally symmetrical nystagmus with compensatory slow phases. Response asymmetry of the slow-phase velocity of the desaccaded and averaged eye position signal was less than 13% in normals (n = 21). Before surgery, patients’ responses were mostly symmetrical. Postoperatively, responses were diminished or absent with head acceleration towards the operated ear in all patients, causing a marked asymmetry which averaged 56% after correction for spontaneous nystagmus. On follow-up, responses regained symmetry. Thus, early after vestibular nerve section, a single utricle produces a normal LVOR only with ipsilateral head translation. Therefore, afferents for the LVOR seem to originate from the mid-lateral area of the macula, where hair cells are stimulated in their on-direction during ipsilateral head translation. Compensation may depend on recovery of the off-directional responses from lateral hair cells of the remaining utricle.

Notes: Abstract  This study assessed whether stationary auditory information could affect body and head sway (as does visual and haptic information) in sighted and congenitally blind people. Two speakers, one placed adjacent to each ear, significantly stabilized center-of-foot-pressure sway in a tandem Romberg stance, while neither a single speaker in front of subjects nor a head-mounted sonar device reduced center-of-pressure sway. Center-of-pressure sway was reduced to the same level in the two-speaker condition for sighted and blind subjects. Both groups also evidenced reduced head sway in the two-speaker condition, although blind subjects’ head sway was significantly larger than that of sighted subjects. The advantage of the two-speaker condition was probably attributable to the nature of distance compared with directional auditory information. The results rule out a deficit model of spatial hearing in blind people and are consistent with one version of a compensation model. Analysis of maximum cross-correlations between center-of-pressure and head sway, and associated time lags suggest that blind and sighted people may use different sensorimotor strategies to achieve stability.

Notes: Abstract  The present study characterizes expression of calbindin D28 K (CB-D28 K) and parvalbumin (PV) in ventral forebrain (VFB) grafts placed in the neocortex of adult rats bearing quisqualic acid lesions to the nucleus basalis magnocellularis. Three to nine months after transplantation surgery, rats were killed for in situ hybridization with probes to CB-D28K or PV and for immunohistochemistry with antibodies to CB-D28K or PV. In addition, an antibody to choline acetyltransferase (ChAT) was used to characterize the cholinergic component in the graft and an antibody to tyrosine hydroxylase (TH) to explore catecholaminergic innervation of the graft. Quantitative analysis of CB-D28K and PV messenger ribonucleic acid (mRNA) was based on counts of silver grains generated by emulsion autoradiography. Cells expressing CB-D28K mRNA were significantly larger than such cells in the adult VFB and the mean number of silver grains per cell was significantly greater than to such cells in the adult VFB. The level of CB-D28K mRNA expression as calculated by ratio of silver grains per unit area was also significantly increased. Quantification of PV mRNA showed no significant differences between the cells in the graft and in the adult VFB. In order to begin to interpret these findings, a comparison was made with such cells in the VFB of developing rats. Brain sections were sampled from embryonic day 17 and postnatal days 1, 5, 12, 19 and adult (6–12 months of age). Cells expressing CB-D28K mRNA were detected in ventral forebrain from postnatal day 5 and cells expressing PV mRNA were detected in ventral forebrain from postnatal day 19. In the course of normal development of the ventral forebrain, no CB-D28K cells were found that were as large or expressed such high levels of CB-D28K mRNA as observed in the grafts. We conclude that changes in grafted cells expressing CB-D28K do not reflect an arrest of developmental processes. TH immunohistochemistry revealed lack of catecholaminergic innervation of the graft, whereas adult mediolateral septal cells that express CB-D28K receive such innervation in addition to other neurotransmitter inputs. Imbalance in neurotransmitter inputs to grafted cells expressing CB-D28K is discussed as a possible factor in their increased size and gene expression.

Notes: Abstract  CO2 laser pulses selectively excite A-δ and C mechano-thermal nociceptors in the superficial layers of the skin. To study the jaw-opening reflex elicited by a purely nociceptive input, we delivered laser pulses to the perioral region in 15 subjects. Sensory threshold was very low (9 mJ/mm2). High-intensity noxious laser pulses (more than 4 × sensory threshold) evoked a single phase of electromyogram suppression (laser silent period, LSP) at an onset latency of 70 ms in the contracted masseter and temporal muscles, bilaterally. Even maximum-intensity laser pulses failed to activate the suprahyoid muscles. The recovery curves to paired laser stimuli showed that at short interstimulus intervals the test LSP was strongly suppressed. At about 380 ms it recovered to 50%, i.e. its recovery curve resembled that of the masseter late silent period after electrical mental nerve stimulation (SP2). In experiments studying the interaction with heterotopic stimuli and non-nociceptive responses, chin-taps or electrical shocks delivered to the supraorbital, infraorbital or mental nerves before laser stimulation strongly suppressed the LSP. A preceding perioral laser pulse strongly suppressed the masseter SP evoked by supraorbital stimulation and the SP2 evoked by mental stimulation, but left SP1 unaffected. We conclude that the perioral A-δ fibre input elicits a jaw-opening reflex simply by inhibiting the jaw-closers. The LSP response is mediated by a multisynaptic chain of brainstem interneurons and shares with the masseter SP2 part of the central circuit in the ponto-medullary region. We also propose that a common centre processes the various inputs for jaw opening.

Notes: Abstract  This paper describes the transport and grasp kinematic parameters associated with four initial hand postures (palm flat and thumb against the hand, palm flat and thumb extended laterally, index and thumb in opposition, and index and thumb in opposition and elbow flexed 90°). A group of healthy adult subjects reached for and picked up a wooden dowel placed midsagittally, at one of three distances (20 cm, 25 cm and 30 cm). The initial posture of the hand and arm altered transport (peak velocity and peak negative acceleration) as well as grasp (peak angle and time to peak angle) parameters, particularly when the elbow was flexed 90°. The pattern of results was reproduced in a pointing paradigm. The findings are discussed in the context of joint space models of reaching.

Notes: Abstract  Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.

Notes: Abstract  We examined motor unit (MU) discharge properties (mean interspike interval, ISI, discharge variability, short-term synchronization, common drive) and force tremor in the first dorsal interosseous (FDI) muscle of five musicians (skill-trained), five weight-lifters (strength-trained) and six untrained subjects during low-force isometric abduction of the index finger. Mean MU ISI was slightly shorter in skill-trained subjects than in untrained subjects. Discharge variability of FDI MUs did not differ significantly between groups. The mean strength of MU synchronization (expressed as the frequency of extra synchronous discharges above chance) was different in skill-trained (0.22±0.02 s–1, 162 MU pairs), untrained (0.32±0.02 s–1, 199 MU pairs) and strength-trained subjects (0.44±0.03 s–1, 183 MU pairs). FDI MU synchrony was weak and of equivalent strength in both hands of skill-trained subjects and the dominant (skilled) hand of untrained subjects. The stronger FDI MU synchrony in the non-dominant hand of untrained subjects was equivalent to that found in both hands of strength-trained subjects. The extent of common modulation of firing rates (common drive) was assessed for a subset of MU pairs and was weaker in skill-trained subjects (0.30±0.04, n=14) than untrained (0.43±0.3, n=14) and strength-trained (0.48±0.03, n=21) subjects. Force tremor was quantified for each hand in the same subjects during isometric index finger abduction at target forces of 0.5 N and 3.5 N. Tremor rms amplitude and peak power in the force frequency spectrum were significantly lower in skill-trained subjects than strength-trained subjects with the 3.5-N target force. The peak tremor frequency was similar in the three groups. The relatively more independent discharge of pairs of FDI MUs in skill-trained subjects was not responsible for the reduced tremor amplitudes in these subjects. Correlations between the overall extent of MU synchrony and common drive in FDI muscles and tremor measures obtained during the same experimental session were all non-significant. Differences in the central descending command signals are the most likely explanation for the more independent discharge of FDI MUs in skill-trained hands, while neural or peripheral muscular factors may be responsible for the weaker tremor.

Notes: Abstract  Activated microglia play an important role in the rejection of intracerebral grafts and the degeneration of axotomized neurones. We studied the effect of macrophage migration stimulatory factor (MSF) or macrophage migration inhibitory factor (MIF) on allogeneic foetal mesencephalic dopaminergic grafts transplanted into the striatum of 6-hydroxydopamine-lesioned rats. Rotation testing revealed a significant compensation of lesion-induced motor asymmetry 3 weeks post-grafting in animals treated with MIF and vehicle-treated controls compared with pre-graft values (Student′s t-test, P≤0.005) and MSF-treated animals (ANOVA, post hoc Fisher PLSD test, P≤0.05). The MSF group showed no significant compensation. Graft recipients with MIF application (1452.06 ± 164.32 tyrosine hydroxylase-positive ventral mesencephalic cells) and controls (1753.21 ± 165.51 tyrosine hydroxylase-positive neurones) displayed good graft survival. Animals with MSF application showed a significant reduction of tyrosine hydroxylase-positive grafted cells (MSF 570.36 ± 209.49 cells) and graft volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD test, P≤0.05). The propotional area of microglia was significantly reduced in MIF animals compared with control animals (ANOVA, post hoc Fisher PLSD test, P≤0.001). Activated microglia and macrophages were reduced by half in the MIF-treated group compared with MSF animals and controls. We conclude that intrastriatal injections of MSF result in impaired function and survival of allogeneic ventral mesencephalon (VM) grafts 3 weeks after transplantation. MIF can reduce the number of microglia and macrophages in allogeneic foetal VM grafts. A reduction of microglia via MIF application did not enhance graft function and survival.

Notes: Abstract  In rabbit and rat retinae, wholemounted preparations and 40 μm thick vibratome sections were processed for nitric oxide synthase (NOS) immunoreactivity and consecutive semithin sections were immunostained with anti-NOS and anti-GABA antisera, respectively. Two types of NOS-labelled amacrine cells were identified: type 1 cells with larger somata were intensely stained, and type 2 cells with smaller somata were weakly stained. A few displaced amacrine cells also showed NOS-like immunoreactivity. All these NOS-like immunoreactive neurons also expressed GABA-like immunoreactivity. Thus, nitric-oxide-containing neurons might constitute a subpopulation of GABAergic neurons in rabbit and rat retinae.

Notes: Abstract  Anticipatory smooth pursuit before the expected appearance of a moving target can reduce the initial retinal blur caused by the 100-ms delay of visual feedback. Humans, though, can only voluntarily generate smooth velocities up to about 5°/s without a moving target. However, previous experiments have shown that repetitive brief presentations of a moving target every few seconds appear to charge an internal store, the contents of which can later be released to generate higher velocity anticipatory movements. This store’s longevity was assessed here by repetitively presenting a moving target for 500 ms at different known intervals up to 7.2 s. Target motion at 25°/s or 50°/s was tested, with presentations in alternate directions or the same direction. Anticipatory velocity, measured 100 ms after target onset, decreased with increasing interval for all target motion conditions. A decrease was still seen when accurate timing cues were given before each presentation, suggesting that the drive for anticipatory pursuit is held in a short-term store lasting a few seconds which can enhance the low velocities produced by volition alone. The results also demonstrate that high-velocity anticipatory pursuit helps to overcome the temporal delays in the system and allows target velocity to be matched at an earlier time.

Notes: Abstract  We examined the lower-limb electromyographic (EMG) activity from a patient with clinically complete spinal cord injury during orthotic gait. A newly developed gait orthosis was used to obtain bipedal locomotion. The surface EMG data during the gait together with the biomechanical variables were collected by way of a radio EMG system. A cyclic EMG activation pattern corresponding to the gait cycles were observed in each of the paralyzed lower-limb muscles during the orthotic gait. Although the EMG activation did not seem to contribute toward generating the gait, it showed some similarities to that of the infant stepping or immature gait. These results might be regarded as one of the indirect pieces of evidence that suggest the existence of a spinally originating motor mechanism underlying human locomotion.

Notes: Abstract  Studies on the proactive control of gait have shown that proximal (hip/trunk) muscles are the primary contributors to balance control, while studies on reactive balance control during perturbed gait, examining only activity in distal (leg/thigh) muscles, have shown that these muscles are important in compensating for a gait disturbance. This study tested the hypothesis that proximal muscles are also primary contributors to reactive balance control during perturbed gait. Thirty-three young adults participated in a study in which an anterior slip was simulated at heel strike by the forward displacement of a force plate on which they walked. Surface electromyographic data were recorded from bilateral leg, thigh, hip and trunk muscles. Kinematic data were collected on joint angle changes in response to the perturbation. The results did not support the hypothesis that the proximal muscles contribute significantly to balance control during perturbed gait. The proximal muscles did not demonstrate more consistent activation, earlier onset latency, longer burst duration or larger burst magnitude than distal muscles. Moreover, although proximal postural activity was often present in the first slip trial, it tended to adapt away in later trials. By contrast, the typical postural responses exhibited by young adults consisted of an early (90–140 ms), high-magnitude (4–9 times muscle activity during normal walking) and relatively long duration (70–200 ms) activation of bilateral anterior leg muscles as well as the anterior and posterior thigh muscles. Thus, postural activity from bilateral leg and thigh muscles and the coordination between the two lower extremities were the key to reactive balance control and were sufficient for regaining balance within one gait cycle. The adaptive attenuation of proximal postural activity over repeated trials suggests that the nervous system overcompensates for a novel balance threat in the first slip trial and fine-tunes its responses with experience.

Notes: Abstract  The relative levels of guanine nucleotide-binding protein α-subunits Gi1α, Gi2α, Gi3α, Goα, Gsα, and Gx/zα were measured in neocortex removed at surgery from patients with intractable temporal lobe epilepsy. Immunoreactivity was quantified using specific polyclonal antisera against the Gα-subunits according to the Laurell “rocket” immunoelectrophoresis technique. We compared the G protein contents of spiking (active) and nonspiking (nonactive) cortical regions, based on intraoperative electrocorticography, within the same and different patients. There were no clear trends for lower or higher levels of G-protein subtypes to be found in the samples of protein extracts from nonspiking regions as compared to spiking regions. However, comparison of paired samples of spiking and nonspiking cortex within the same patient demonstrated that levels of certain G-protein subtypes were either increased or decreased in all patients. This indicates that cortical regions with enhanced neuronal activity may produce microzonal alterations in the levels of G proteins. Moreover, our results suggest that high levels of Gi1α and low levels of the other G-protein subtypes appear to be associated with a greater susceptibility to maintaining spiking activity.

Notes: Abstract  Neuropeptide FF (NPFF, F8Famide) is best known for its modulating effect on opioid analgesia and morphine tolerance. However, the exact mode of action of NPFF in sensory transmission is not known. We compared the distribution of NPFF-immunoreactive (ir) fibers and terminal-like thickenings with the retrograde, tracer-filled spinothalamic (ST) neurons in the lateral spinal nucleus (LSN) and lateral cervical nucleus (LCN) of rat, areas where NPFF-containing nerve terminals are abundant. We injected fluorescent latex microspheres into the ventroposterolateral thalamic nucleus and more medial thalamic nuclei, which are innervated by ST neurons. We found NPFF-ir terminal-like thickenings and fibers apposing the tracer-filled neurons in the LSN and LCN. ST neurons filled with the retrograde tracer making contacts with NPFF-ir terminal-like thickenings, were found to terminate not only in the ventroposterolateral thalamic nucleus but also in more medial thalamic nuclei. The highest number of tracer-filled ST neurons having NPFF-ir terminal-like thickenings and fibers in apposition were found at the cervical level. Our results suggest that NPFF-containing systems in the spinal cord of rat are not limited to the substantia gelatinosa, and the sensory functions of NPFF may be mediated at least partly through the modulation of the ST system. NPFF-ir contacts in the LSN and LCN might play an important role in the somatic sensory transmission system. This study shows evidence for the first time that the spinal NPFF-containing system may be involved in mechanisms that control sensory input to the supraspinal levels.

Notes: Abstract  We evaluated the effects of systemic administration of a low dose of naloxone in rats with bilateral lesions in the area of the locus coeruleus (LC) under conditions of unilateral inflammation, compared with those in sham-operated rats. In each group, rats received a single s.c. injection of carrageenan (6 mg in 0.15 ml saline), and effects of a low dose of naloxone (5 μg/kg, i.p.) on thermal nociception were examined at 4 h and 7 days following the induction of unilateral hindpaw inflammation. The antinociceptive effect was assessed by prolongation of the paw withdrawal latency (PWL) to noxious thermal stimuli. Prior to induction of inflammation, the low dose of naloxone had no significant effect on PWLs in either the sham-operated or the LC-lesioned rats. Four hours after carrageenan injection, the low dose of naloxone produced prolongation of PWLs in the sham-operated rats but failed to induce antinociception in the LC-lesioned rats. Antinociceptive effects were observed in both groups of rats 7 days after carrageenan injection. These results suggest that the LC is involved in naloxone-induced antinociception during the early phase of inflammation.

Notes: Abstract  Electromyographic (EMG) patterns of leg muscles associated with rapid body sway were studied in relation to displacement of the center of foot pressure (CFP). Standing subjects were instructed to shift the CFP by swaying their bodies, pivoting at the ankle as rapidly and accurately as possible after an auditory signal. CFP position was designated as N when the subject maintained a relaxed bending posture and as F when a maximally forward-leaning posture was maintained. A serial, stereotyped triphasic EMG pattern was observed in the rapid shift of CFP from N to F: cessation of EMG activity in the gastrocnemius (GC) muscle was followed by a burst in the tibialis anterior (TA) muscle (acceleration phase), and then resumed discharge occurred in the GC muscle with cessation of activity in the TA muscle (deceleration and stop). When the subject shifted the CFP from N to F to different degrees, the duration and amount of EMG activity in the TA muscle during acceleration and the GC muscle in deceleration were proportionate to the amount of CFP displacement associated with forward body sway. To determine the functional roles of sensory inputs from the foot on the triphasic EMG pattern, body sway was studied under the condition of sensory block in the feet induced by ischemia from tourniquets placed bilaterally just above the ankle joints. The triphasic EMG pattern persisted during ischemia. The time of GC cessation and the onset of TA burst at acceleration remained unchanged, but the times of TA cessation and resumption of GC discharge at deceleration were altered during ischemia. Moreover, subjects were unable to stop at F and eventually fell. These results indicate that both amount and duration of EMG activity associated with rapid body sway are functions of the amount of CFP displacement. Somatic sensation from the feet is important for control of burst and cessation timing and duration in leg muscle activity.

Notes: Abstract  Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37±0.5°C) and hypothermic (30±0.5°C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.

Notes: Abstract  The purpose of this study was to determine the precision of proprioceptive localization of the hand in humans. We derived spatial probability distributions which describe the precision of localization on the basis of three different sources of information: proprioceptive information about the left hand, proprioceptive information about the right hand, and visual information. In the experiment subjects were seated at a table and had to perform three different position-matching tasks. In each task, the position of a target and the position of an indicator were available in a different combination of two of these three sources of information. From the spatial distributions of indicated positions in these three conditions, we derived spatial probability distributions for proprioceptive localization of the two hands and for visual localization. For proprioception we found that localization in the radial direction with respect to the shoulder is more precise than localization in the azimuthal direction. The distributions for proprioceptive localization also suggest that hand positions closer to the shoulder are localized more precisely than positions further away. These patterns can be understood from the geometry of the arm. In addition, the variability in the indicated positions suggests that the shoulder and elbow angles are known to the central nervous system with a precision of 0.6–1.1°. This is a considerably better precision than the values reported in studies on perception of these angles. This implies that joint angles, or quantities equivalent to them, are represented in the central nervous system more precisely than they are consciously perceived. For visual localization we found that localization in the azimuthal direction with respect to the cyclopean eye is more precise than localization in the radial direction. The precision of the perception of visual direction is of the order of 0.2–0.6°.

Notes: Abstract  A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below threshold for obtaining electromyographical (EMG) responses in active hand muscles can suppress responses evoked in the same muscles at rest by a suprathreshold magnetic test stimulus given 1–5 ms later. In order to define the mechanism of this inhibitory effect, we recorded descending volleys produced by single and paired magnetic transcranial stimulation of motor cortex through high cervical, epidural electrodes implanted for pain relief in two conscious subjects with no abnormality of the central nervous system. The conditioning stimulus evoked no recognisable descending activity in the spinal cord, whilst the test stimulus evoked 3–4 waves of activity (I-waves). Conditioning stimulation suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus. Inhibition of the descending spinal volleys was most pronounced at ISI 1 ms and had disappeared by ISI 5 ms. It was evident for all components following the I1-wave, while the I1-wave itself was not inhibited at all. We conclude that a small conditioning magnetic stimulus can suppress the excitability of human motor cortex, probably by activating local cortico-cortical inhibitory circuits.

Notes: Abstract  The aim of this study was to test Bernstein’s idea that motor synergies provide solutions to the motor redundancy problem. Forces produced by individual fingers of one hand were recorded in one-, two-, three-, and four-finger tasks. The subjects (n=10) were asked to produce maximal total force (maximal voluntary contraction, MVC) and to match a ramp total force profile using different combinations of fingers. We found that individual finger forces were smaller in multifinger MVC tasks than in single-finger tasks. The deficit increased with the number of fingers involved. A saturation effect was observed: when several effectors were involved, adding a new effector did not significantly change the total force output. The data confirmed the idea that the central neural drive arriving at the level of synergies has a certain limit, a ceiling, that cannot be exceeded. The central nervous system cannot maximally activate the muscles serving all the fingers at the same time. Secondly, during the course of ramp trials, forces produced by individual fingers were linearly related to each other. Hence, a force sharing pattern was established at the beginning of the trial and did not change during the ramp period. A hypothesis is suggested that force distribution among fingers may be organized so as to minimize unnecessary rotational moment with respect to the functional longitudinal axis of the hand. Finally, in the four-finger trials, variance of the total maximal force output in ten consecutive attempts was smaller than the sum of variances of the maximal individual finger forces. The finding suggests that the control system of the motor tasks studied involves at least two levels, a central neural drive level and a synergy level. At the synergy level, an intercompensation in individual finger force production is observed.

Notes: Abstract  We have previously reported that grafting of fetal ventral mesencephalic (VM) tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF) injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase (TH) immunoreactivity. In this study, we investigated the electrochemical indices of dopamine (DA) release in these grafted animals in the striatum and nigra. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. One to two months after 6-OHDA administration, fetal VM tissues were grafted in the lesioned nigral area followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals receiving transplantation and GDNF, but not BDNF or PBS, injection showed a significant decrease in rotation 1–3 months after grafting. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate DA overflow in the striatum. We found that 6-OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane-anesthetized rats. Three months after GDNF-bridged grafting, application of KCl elicited DA release both in nigra and striatum. The KCl-evoked DA release area was limited to the GDNF-bridging tract in the striatum. On the other hand, KCl did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical studies indicated that TH-positive neurons and fibers were found in the nigra and striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal nigral transplantation and GDNF injection may restore the nigrostriatal DA pathway and DA release in these hemiparkinsonian animals and support the hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA neurons.

Notes: Abstract  Head tilt is a rotation of the head relative to gravity, as exemplified by head roll or pitch from the natural upright orientation. Tilt stimulates both the otolith organs, owing to shifts in gravitational orientation, and the semicircular canals in response to head rotation, which in turn drive a variety of behavioral and perceptual responses. Studies of tilt perception typically have not adequately isolated otolith and canal inputs or their dynamic contributions. True tilt cannot readily dissociate otolith from canal influences. Alternatively, centrifugation generates centripetal accelerations that simulate tilt, but still entails a rotatory (canal) stimulus during important periods of the stimulus profiles. We reevaluated the perception of head tilt in humans, but limited the stimulus to linear forces alone, thus isolating the influence of otolith inputs. This was accomplished by employing a centrifugation technique with a variable-radius spinning sled. This allowed us to accelerate the sled to a constant angular velocity (128°/s), with the subject centered, and then apply dynamic centripetal accelerations after all rotatory perceptions were extinguished. These stimuli were presented in the subjects’ naso-occipital axis by translating the subjects 50 cm eccentrically either forward or backward. Centripetal accelerations were thus induced (0.25 g), which combined with gravity to yield a dynamically shifting gravitoinertial force simulating pitch-tilt, but without actually rotating the head. A magnitude-estimation task was employed to characterize the dynamic perception of pitch-tilt. Tilt perception responded sluggishly to linear acceleration, typically reaching a peak after 10–30 s. Tilt perception also displayed an adaptation phenomenon. Adaptation was manifested as a per-stimulus decline in perceived tilt during prolonged stimulation and a reversal aftereffect upon return to zero acceleration (i.e., recentering the subject). We conclude that otolith inputs can produce tilt perception in the absence of canal stimulation, and that this perception is subject to an adaptation phenomenon and low-pass filtering of its otolith input.

Notes: Abstract  To understand the internal representations used by the nervous system to coordinate multijoint movements, we examined the coordination among the body segments during reach-to-grasp movements which involve grasping by the hand and reaching by the arm and trunk. Subjects were asked to reach and grasp an object using the arm only, the trunk only, and some combinations of both arm and trunk. Results showed that kinematic parameters related to the transport component of the arm and the trunk, such as peak velocity and time to peak velocity, varied across conditions and that the coordination pattern between the arm and trunk was different across conditions. However, parameters related to the grasp component, such as peak aperture, time to peak aperture, and closing distance, were invariant, regardless of whether the hand was delivered to the target by the arm only, the trunk only, or both. We hypothesize that a hierarchy of motor control processes exists, in which the reach and grasp components are governed by independent neuromotor synergies, which in turn are coordinated temporally and spatially by a higher-level synergy.

Notes: Abstract  The density of substance P (SP)-, calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) nerve endings was quantitatively evaluated in intact and inflamed gastrocnemius-soleus muscle of the rat. In persistently inflamed muscle (12 days after a single injection of Freund’s adjuvant into the muscle), the density of SP-ir fibres was significantly increased. CGRP- and VIP-ir fibres displayed an insignificant increase in density. The density of fibres ir for nerve growth factor (NGF) and for growth-associated protein 43 (GAP-43/B-50), a marker for axonal sprouting, regeneration and synaptic reorganisation, increased significantly in persistently inflamed muscle. The data are consistent with the established contribution of NGF on the expression of SP and GAP-43 in afferent neurones under the influence of a persistent inflammation.

Notes: Abstract  The cortical forepaw area of young adult rats was mapped by recording the response properties of small clusters of neurons in layer IV of the primary somatosensory (SI) cortex. First we quantitatively analyzed the somatotopic organizational features of the cortical forepaw representation in terms of areal extent and topography, receptive field (RF) sensory modality, size, and location. We also assessed the influence of environmental enrichment, known to induce structural alterations in cortical connectivity, on the representational characteristics of the forepaw maps. Long-Evans rats were housed in environments (standard, SE; enriched, EE) promoting differential tactile experience for 71–113 days from weaning. Within the SI, we found a single and complete topographic map of the cutaneous surfaces of the forepaw consisting of a rostrolateral-caudomedial sequence of digit and pad representational zones. Small islets of noncutaneous responses (NCR; high-threshold, deep-receptor input) within the boundaries of the cutaneous maps were a conspicuous feature of the forepaw map for SE rats. These islets created discontinuities in the representation of contiguous skin territories. In the SE rats, about 79% of the cortical sites activated by light tactile stimulation had a single cutaneous RF, whereas about 21% exhibited multiple RFs. Most single-digit RFs we delineated in the SE rats extended across two or three phalanges. As a result, the representations of the phalangeal skin surfaces were not segregated but formed an overlapping continuum. Moreover, within these regions, as the electrode was displaced in regular steps across the mediolateral axis, RFs did not shift across the digit skin surface in an orderly manner, suggesting a lack of internal topography in the finger representation zones. Tactile experience promoted by environmental enrichment induced alterations in the representational features of the SI cutaneous map of the forepaw. In EE rats, the areal extent of the forepaw cutaneous representation was 1.5 times larger than in SE rats. Indeed, the cutaneous map extended into NCR cortical sectors along its external margins and also into NCR islets found in the forepaw area. Consequently, in EE rats there were fewer representational discontinuities. The areal enlargement was due to a selective increase in the areal extent of the glabrous but not the hairy skin surface representations. Furthermore, protuberant glabrous skin (digit tips, palmar pads) was represented over larger cortical regions than were other glabrous skin territories less likely to be stimulated during object palpation and manipulation. Maps from EE rats were also characterized by a larger proportion of sites with single RFs (88% compared with 79%). In addition, glabrous RFs from EE rats were smaller and more clustered on the digit tips and palmar pads than were RFs in SE rat maps. RF size on hairy skin surfaces remained unchanged. Because the RFs were smaller, the cutaneous maps of EE rats contained distinct representations of digit phalangeal glabrous skin. RFs tended to exhibit more orderliness in their progression across the digit glabrous skin of EE rats than they did in SE rats. The phalanges of EE rats were represented in distinct patches. Neurons in EE rats were more sensitive to light tactile stimulation than were neurons in SE rats. These alterations were presumably mediated by the selective potentiation of cutaneous over deep-receptor activation. More generally, the present study corroborates the view that cortical cutaneous maps are maintained in a permanent state of use-dependent fluctuation.

Notes: Abstract  Two-limb coordination of homologous and non-homologous effectors was examined during isofrequency (1:1) and multifrequency (2:1) conditions. The coordination patterns involved flexion and extension movements in the sagittal plane and were performed under unloaded and single-limb (right arm) loaded conditions. Previous studies suggested that the lower degree of 1:1 synchronization observed during nonhomologous as compared to homologous coordination results from natural differences in biophysical (inertial) properties. Elaborating on this idea, adding weight to the right arm was hypothesized to modulate its inertial characteristics, rendering homologous limbs more dissimilar and nonhomologous limbs more similar by enhancing and decreasing their inertial differences, respectively. Therefore, the observations made during unloaded conditions were predicted to be completely reversed during loaded conditions. Findings revealed that during 1:1 coordination (experiment 1) single-limb loading resulted in a decreased relative phase stability, whereas relative phase accuracy depended upon the limb combination. In particular, phase-locking was more accurately maintained for loaded homologous than for nonhomologous limbs, whereas loading the nonhomologous limbs resulted in a deterioration of the quality of synchronization. These findings suggest that there is an additional explanation of differential coordination capabilities among limb combinations. It is hypothesized that the neural networks subserving the control centers of the homologous limbs are more tightly connected than those of the nonhomologous effectors, allowing 1:1 synchronization to be more successfully preserved in the face of (load) perturbations. During 2:1 coordination (experiment 2), the loading procedure disturbed the coordination dynamics across all limb combinations. That no differential effect of loading on effector combination was observed is possibly a result of the fact that only an initial level of practice was studied in which optimal relative phase dynamics are still being explored for both homologous and nonhomologous limbs.

Notes: Abstract  Lattice-like perineuronal accumulations of extracellular-matrix proteoglycans have been shown to develop during postnatal maturation and to persist throughout life as perineuronal nets (PNs) in many brain regions. However, the dynamics of their reorganization in adults are as yet unknown. The aim of the present study was to examine the capability of PNs for reconstitution after experimental destruction and to search for possible consequences of extracellular-matrix degradation for neurons and glial cells. The changes were induced by single intracortical injections of Proteus vulgaris chondroitinase ABC and studied after postinjection periods of 1 day to 5 months. The N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA), an antibody against chondroitin-sulphate proteoglycans, three antibodies recognizing initial chondroitin or chondroitin-sulphate moieties (’stubs’) of proteoglycan core proteins, an antibody against the hyaluronan-binding protein component of versican, and biotinylated hyaluronectin, which binds to hyaluronan, were used as cytochemical markers. One day postinjection, the WFA-binding sites and hyaluronan were shown to be almost completely removed within a circumscribed digestion zone. The staining of different core-protein components revealed only fragments of PNs. These changes were found to be partly compensated 4 weeks after injection of chondroitinase ABC. After 8 and 12 weeks postinjection, the cytochemical and structural characteristics as well as the area-specific distribution patterns of PNs were progressively reconstituted. At 5 months postinjection, they could not be distinguished from those in untreated tissue. In contrast to such transient changes, a diffuse chondroitin-sulphate proteoglycan immunoreactivity persisted in the neuropil. Loss of neurons or alterations of their structure as well as reactions of glial cells were not observed. We conclude from this study that PNs, enzymatically destroyed in the adult rat brain, can be completely reconstituted, but the restoration of their extracellular-matrix components needs several months.

Notes: Abstract  Muscle pain generally has an inhibitory effect on voluntary orofacial motor function. However, it is not known whether muscle pain causes direct or indirect changes in motoneuron excitability. In this study a monopolar needle stimulation technique was used to evoke the direct motor response (M-response) in the left masseter muscle and the heteronymous H-reflex in the left temporalis muscle as an indirect measure of motoneuron excitability. Series of 20 repeated electrical stimuli were delivered at 50% of maximal voluntary contraction (MVC) before, during, and after periods with experimental jaw-muscle pain in 11 healthy subjects. Pain was induced by standardized infusion of hypertonic (5%) saline into the mid-portion of the right masseter muscle. The mean pain intensity rating on a 100-mm visual analog scale was 42±5 mm. The short-latency responses (less than 6 ms) could be evoked in all subjects. Analysis of the latency and amplitude of the temporal H-reflex indicated no significant effect of jaw-muscle pain. The amplitude of the masseteric M-response was significantly smaller in the postpain condition than in the pain conditions (ANOVA, P=0.018), but no differences were found between the prepain and postpain conditions. In nine subjects, poststimulus periods (mean offset latency, 69.6±8.6 ms) with significantly (more than 50%) suppressed EMG activity were detected in the ipsilateral masseter muscle following the M-response (mean offset latency, 5.5±0.2 ms). These reflex responses did not show a systematic change during the pain conditions. In conclusion, acute contralateral jaw-muscle pain does not seem to modulate the motoneuron excitability as measured by the heteronymous H-reflex.

Notes: Abstract  We used anterograde and retrograde transsynaptic pathway tracing techniques to reveal the retinal origin and the cortical termination of the expanded retino-geniculo-middle suprasylvian (MS) cortex pathway in adult cats which sustained lesions of areas 17 and 18 on the day of birth (P1) or at 1 month of age (P28). Following anterograde transsynaptic transport of tritiated amino acids from the eye, four major results were obtained: (1) a strong and specific pathway from retina through dorsal lateral geniculate nucleus (dLGN) to the posterior half of MS cortex was identified; this pathway is a substantial expansion of an insignificant pathway present in intact cats; (2) the terminus of the pathway was lower layer III and layer IV; (3) contralateral projections were stronger than ipsilateral projections; (4) projections in P28 cats were stronger than those in P1 cats. Following retrograde transsynaptic transport of WGA-HRP from posterior MS cortex, four additional results were obtained: (1) the pathway was enlarged and visuotopically organized; (2) the pathway arose primarily from α- and γ-retinal ganglion cells; (3) a small number of β-cells in P1 cats and a modest number in P28 cats also contribute to the pathway; (4) the combined numbers of γ- and β-cells relative to α-cells was greater in temporal retina than in nasal retina. The combined demonstration of both origin and terminus of the pathway with transsynaptic tracers argued strongly for high levels of coupling between primary and secondary pathway limbs in both P1 and P28 cats. This level of coupling, as well as other features of the pathway, have much in common with the retino-geniculo-17/18 pathway of intact cats. However, the retino-geniculo-MS system in P1 cats transmits primarily Y and W signals, in P28 cats X, Y, and W signals; whereas the retino-geniculo-17/18 pathway transmits primarily X and Y signals. These results have implications for understanding the repercussions of early visual cortex lesions in monkeys and humans.

Notes: Abstract  Using light microscopy and immunocytochemistry, we investigated the morphological changes of retinal tissues and the reaction of Müller cells in the ischemic rat retina induced by increasing intraocular pressure. At early stages (from 1 h to 24 h after reperfusion), cells in the ganglion cell layer and in the inner nuclear layer showed some degenerative changes, but at later stages (from 72 h to 4 weeks) marked degenerative changes occurred in the outer nuclear layer (ONL). At 4 weeks after reperfusion, the ONL was reduced to 1 or 2 cell layers. Immunoreactivity for glial fibrillary acidic protein (GFAP) appeared in the endfeet and distal processes of Müller cells as of 1 h after reperfusion. GFAP immunoreactivity in Müller cells increased up to 2 weeks and then decreased at 4 weeks after reperfusion. Our findings suggest that Müller cells are involved in the pathophysiology of retinal ischemia through the expression of GFAP. The degree of GFAP expression in Müller cells closely correlated with that of the degeneration of retinal neurons.

Notes: Abstract  Transient visual field defects (VFDs) and phosphenes were induced in normal volunteers by means of transcranial magnetic stimulation (TMS) using a circular magnetic coil of 12.5 cm diameter placed with its lower rim 2–4 cm above the inion in the midline. Subjects had to detect small, bright dots presented randomly for 14 ms in one of 60 locations on a computer screen resulting in a plot of the central 9° of the visual field. In 8 of 17 subjects, transient VFDs were inducible at peak magnetic field strenghts of 1.1–1.4 T. In the central 1–3°, detection of targets was impaired in both the upper and lower visual field, whereas at 4–9° large parts of only the lower visual field were affected with a sharp cut-off along the horizontal meridian. Targets at 1° in the lower field were affected with lower TMS intensities than corresponding locations in the upper or peripheral locations in the lower field. Detection of central targets was affected at more caudal stimulation sites than detection of peripheral targets. Phosphenes were elicitable in 14 of 17 subjects at clearly lower field strengths of 0.6–1.0 T. Many subjects perceived chromatophosphenes. From a discussion of the literature on patients with VFDs and the known topography of the human visual system, it is concluded that the transient VFDs at 1–3° are probably due to stimulation of both striate cortex (V1) and extrastriate areas (V2/V3), while VFDs in the lower visual field at eccentricities 4–9° are due to stimulation of V2/V3 but not V1.

Notes: Abstract  Studies of rapid, single degree-of-freedom movements have shown different changes in electromyographic patterns for movement tasks that appear very similar (e.g., movements over different ranges of distance). However, it is not clear whether these differences are a result of joint-specific control schemes or whether they are instead due to the limited range of task parameters studied relative to the mechanical constraints of each joint (e.g., short compared with long movements relative to the range of motion of a particular joint). In this study, we measured and compared the kinematic trajectories and electromyograms recorded during various movement tasks at the wrist, elbow, and ankle. Subjects performed movements over a wide range of distances “as fast as possible,”“at a comfortable speed,” and against two inertial loads (at the elbow only), and they performed movements over a fixed distance at three different speeds at the wrist and ankle. For fast movements we show that, in spite of some joint-specific differences, the basic pattern of electromyographic (EMG) modulation is similar at all three joints; for example, the agonist EMG burst transitions from a fixed duration to an increasing duration with increasing movement distance at all three joints. Moreover, the distance at which this transition occurs in one joint relative to the distance at which this transition occurs in the other two joints is consistent across subjects. The transition occurs at the shortest distance at the ankle and the longest distance at the wrist. In general we suggest that the data are consistent with a single set of control rules applied at all three joints, with the biomechanical constraints at each joint accounting for the differences in the EMG and kinematic patterns observed across joints.

Notes: Abstract  Investigations of pain using functional imaging techniques have revealed an extensive central network associated with nociception. This network includes the thalamus, insula, prefrontal cortex and anterior cingulate cortex (ACC) as well as the somatosensory cortices. Positron emission tomography (PET) of regional cerebral blood flow (rCBF) has demonstrated activation of the ACC during cognitively challenging tasks such as the Stroop interference task and divided attention. One interpretation of this research is that ACC is involved in the general features of attention and that it does not play a specific role in pain processing per se. Three-dimensional PET imaging provides a method for assessments of rCBF in a single individual during multiple tasks. In addition, coregistration of PET and magnetic resonance (MR) images allows for better localisation of the PET signals so that differences in cortical activation sites can be more accurately determined. This approach was used to assess rCBF during the experience of pain by subtracting images collected during heat from those during noxious heat stimulation. Two regions of the ACC had elevated rCBF, one in the perigenual region and one in the mid-rostrocaudal region (i.e. midcingulate cortex). During the execution of the Stroop task, the group result showed the midcingulate region overlapping with the site seen during the experience of pain. This group result, however, was not confirmed in the individual subject analysis, which revealed widespread and independent areas of ACC response to pain and Stroop. It is concluded that the ACC contributes to multiple cognitive procedures. It is inadequate to describe the primary contribution of ACC to pain processing as “attention” because it is unlikely that the multiple small and independent activation sites produced by pain and Stroop subserve attentive processing throughout the brain.

Notes: Abstract  Previous studies indicate that the withdrawal reflex system in the rat has a “modular” organization, each reflex pathway performing a specific sensorimotor transformation. Here, we wished to clarify which cutaneous receptors contribute to this system and to determine whether there are differences in this respect between reflex pathways of different muscles. Withdrawal reflexes of the peroneus longus, extensor digitorum longus, and semitendinosus muscles were recorded with EMG techniques during high reflex excitability in decerebrate spinal rats (n=26). While maintained innocuous pressure on glabrous skin could elicit a sustained reflex activity in all muscles studied, vibration of glabrous skin (10–300 Hz) always failed to evoke a reflex response, suggesting that slowly adapting, but not rapidly adapting, low-threshold mechanoreceptive fibers from this type of skin contribute to withdrawal reflex pathways. Thermal stimulation in the innocuous range, i.e., cooling from 32 to 17°C, or warming the skin from 32 to 41°C, always failed to produce reflex responses, indicating that neither cold nor warm receptors contribute to withdrawal reflex pathways. When either cooling or warming the skin to the noxious temperatures of 1°C or above 45°C, respectively, a reflex discharge was often evoked in the muscles studied. Intradermal administration of histamine, a potent pruritogenic substance, produced very weak, or no, reflex response. In contrast, mustard oil produced vigorous reflex responses in all muscles studied. These findings suggest that some chemonociceptors contribute only weakly, or not at all, to withdrawal reflex pathways. The present data suggest that a selective set of cutaneous receptors contribute to withdrawal reflex pathways and that different withdrawal reflex pathways receive input from essentially the same cutaneous receptor types.

Notes: Abstract  Electrical stimulation of the Gasserian ganglion resulted in partial depletion of calcitonin gene-related peptide (CGRP) from ipsilateral central terminals of pseudounipolar primary sensory ganglion cells. Affected terminals exhibit decreased CGRP immunoreactivity as shown by cytophotometric densitomery of the caudal trigeminal nucleus. The decrease in CGRP immunoreactivity is statistically significant only in the medial one-third of the caudal trigeminal nucleus. Since earlier studies have shown that electrical stimulation of the Gasserian ganglion induces first accumulation then depletion of CGRP from perivascular sensory terminals in the dura mater, the present experiments suggest that CGRP is depleted also from central terminals of primary sensory trigeminal neurons, which might be of importance in the pathogenesis of migraine headache.

Notes: Abstract  The reflex responses to brisk, ramp stretch perturbations of the human flexor pollicis longus muscle (FPL) were recorded during isometric and slow concentric or eccentric contractions at similar levels of muscle excitation. The subjects flexed their thumb to push down against a thumb-rest, whose position was controlled by a servo-controlled motor. In different runs, the stretch perturbations were imposed when the thumb-rest was stationary (isometric) or was flexing or extending the interphalangeal joint of the thumb at a constant velocity, i.e. during concentric or eccentric contractions of FPL. The latency of the most prominent component of the electromyographic reflex in the isometrically contracting muscle was about 60 ms, measured from the command signal. The amplitude of this response was sharply reduced during the non-isometric contractions. While not dependent on the direction, this modulation of the reflex response increased with the speed of active movement of the interphalangeal joint (flexion or extension). The response was greatly reduced during concentric or eccentric movements as slow as 1.6 mm·s–1 (approximately 5°·s–1 at the joint). When the force rather than the position of the thumb-rest was servo-controlled, the stretch response to perturbation again diminished with speed in a self-paced flexion task, compared with an isometric “hold” condition.

Notes: Abstract  We investigated intermanual transfer and long-term retention of practice-related perceptual learning in the domain of tactile hyperacuity. Subjects discriminated a row of three dots in which the central dot was offset laterally from a row without such offset. Performance at the right index fingerpad improved with practice. Practice effects transferred essentially completely to the left index fingerpad. When tested some months later at the right index fingerpad, long-term retention of learning was limited and further practice was required to stabilize discrimination thresholds. Intermanual transfer of tactile learning appears to be a general phenomenon, while long-term retention appears to be limited in hyperacuity tasks.

Notes: Abstract  Growth factors involved in angiogenesis are critical to both the normal and pathological vascular development in the retina and choroid. In the present experiment, the relationship between the vascular endothelial growth factor (VEGF) expression and the retinochoroidal vasculogenesis in Sprague-Dawley rats was investigated using in situ hybridization and immunohistochemistry. It was found that VEGF was produced mainly by astrocytes and Müller cells in the neural retina, and this was correlated temporally and spatially with the retinal vasculogenesis. In addition, it was observed that, although the VEGF expression in the retinal pigment epithelium (RPE) decreased with increasing age, it persisted from the embryonic stage to adulthood. These findings indicate that the VEGF expression in RPE may play a role in the development of the choroidal vessels as well as in the maintenance of the normal structure and permeability of the choriocapillaris in adults.

Notes: Abstract  Latencies of eye movements to peripheral targets are reduced when there is a short delay (typically 200 ms) between the offset of a central visual fixation point and the target onset. This has been termed the gap effect. In addition, some subjects, usually with practice, exhibit a separate population of very short latency saccades, called express saccades. Both these phenomena have been attributed to disengagement of visual attention when the fixation point is extinguished. A competing theory of the gap effect attributes it to disengagement of oculomotor fixation during the temporal gap. It is known that auditory targets are effective in eliciting saccadic eye movements, and also that covert attention operates in the auditory modality. If the gap effect and express saccades are due to disengagement of spatial attention, both should persist in the auditory modality. However, fixation of gaze is largely under visual control. If the gap effect results from disengagement of fixation, then at least a reduced effect should be seen in the auditory modality. Human subjects performed the gap task and a control task in the dark, using auditory fixation points and saccadic targets, on five successive days. Despite this practice, express saccades were not observed. There was a reliable gap effect, but the reduction in saccadic latency was only 17 ms, compared with 32 ms for the same subjects in the visual modality. This suggests that about half the gap effect is due to disengagement of visual fixation. The remainder was not due to non-specific warning effects and could be attributed to offset of the auditory fixation stimulus.

Notes: Abstract  Rats with lesions either of medial septal nucleus (MSN) or the entorhinal cortex (ECx) were compared postoperatively with unoperated controls in a discrete-trial, delayed matching-to-position (DMTP) task, conducted on an elevated T-maze. A DMTP trial consisted of two consecutive visits to the maze: an information run and a choice run. The animals were first forced to visit a randomly selected choice arm in the information run. In the choice run, the correct response was to match the choice arm that had been visited on the information run, regardless of whether the information run itself had been rewarded or not. MSN animals failed to succeed in this task, performing at close to chance level throughout training. On the other hand, ECx rats consistently perform at a level comparable with that of unoperated controls; both groups attained more than 90% correct after 192 trials. Long-term retention testing was carried out after an intermission of 4 weeks, when the same task was re-administered to the ECx and unoperated control animals. ECx animals showed significantly less saving than controls in the retention test. In contrast, when the retention interval within a DMTP trial was increased by the imposition of a 20-s delay between the information and choice runs, the ECx group was not selectively affected by this manipulation.

Notes: Abstract  We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and nonallodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of μ and δ opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective κ-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal κ-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal μ and δ, but not κ, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal pain-related behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.

Notes: Abstract  It is currently controversial whether auditory events produce inhibition of return (IOR). Although some authors argue that this can arise, others propose that peripheral auditory cues do not produce the characteristic IOR pattern of delayed detection latencies for ipsilaterally presented auditory or visual targets, unless a saccade is made to the cued location. We suggest that these previous discrepancies may depend on whether attention is reoriented centrally following the peripheral sound. We presented spatially uninformative peripheral auditory cues prior to visual targets requiring speeded detection responses. IOR was found in the absence of eye movements, provided an auditory reorienting event was presented at central fixation between onset of the peripheral cue and the subsequent target, but not when the central reorienting event was visual. A subsequent experiment demonstrated that auditory IOR between successive targets is similarly significantly reduced in the absence of an appropriate central reorienting event. These results imply that auditory stimuli can induce IOR directly. Previous failures to demonstrate IOR following auditory cues may have been due to an opposing influence of long-lasting attentional facilitation at the cued location, rather than to the putative inability of auditory stimuli to engage oculomotor processes generating IOR.

Notes: Abstract  To test a potential “gating” effect of noradrenaline (NA) in the auditory cortex, the acoustic threshold was estimated by determining the rate-level function of neurons before, during, and after microiontophoretic application (5–40 nA) of NA. The rationale behind this experiment was that a gating effect should decrease the threshold for acoustic excitatory responses. From 84 recorded neurons, we observed (1) that application of NA increased the threshold for 48 of 84 cells, and (2) that, on average, the slope of the rate-level functions was unchanged. These effects on the threshold are consistent with the fact that the dominant effect of NA on the evoked response is inhibition for 34 of 84 cells; increases in evoked responses were observed for only 14 of 84 cells. GABA application (0–50 nA) also led to increased response threshold for 19 of 24 cells (unaffected, 5 of 24 cells). However, for three cells the effect of GABA application was antagonized by bicuculline application, while on the same cells bicuculline application did not prevent the noradrenergic increase in threshold. The effect induced by NA on the threshold raises questions about the generality of a gating effect of NA in sensory neocortex.

Notes: Abstract  We sought to determine whether an increase in judged egocentric distance created by increasing vergence-specified distance would be negated when participants pointed at their own finger. It was found that ocular position dominates limb proprioception in the judgement of finger distance in the sagittal plane when vision is available. In contrast, an increase in perceived egocentric distance was largely attenuated by the presence of limb proprioception in reduced visual cue conditions. We conclude that the relative contribution of vergence to perceived distance depends upon the strength of the vergence effort signal when there are other cues present. Furthermore, if the distance percept includes a major contribution from retinal cues, then the visual component will dominate the limb proprioception component. If the visual component is largely determined by vergence information, limb proprioception will make a significant contribution and actually dominate when the vergence effort signal is weak. The results extend previous studies that have found a similar relationship between ocular position and limb proprioception in the perception of a finger′s location in the coronal plane.

Notes: Abstract  Normal human subjects were tested for their ability to discriminate the orientation of a square plaque tilted in depth, using two different tasks: a grasping task and a perceptual matching task. Both tasks were given under separate monocular and binocular conditions. Accuracy of performance was measured by use of an opto-electronic motion analysis system, which computed the hand orientation (specifically, a line joining the tips of the thumb and index finger) as the hand either approached the target during grasping or was used to match the target. In all cases there was a very strong statistical coupling between hand orientation and target orientation, irrespective of viewing conditions. However, the matching data differed from the grasping data in showing a consistent curvature in the hand-target relationship, whereby the rate of change of hand orientation as a function of object orientation was smaller for oblique orientations than for those near the horizontal or vertical. The results are interpreted as reflecting the operation of two different mechanisms for analysing orientation in depth: a visuomotor system (assumed to be located primarily in the dorsal cortical visual stream) and a perceptual system (assumed to be located in the ventral stream). It may be that the requirements of visuomotor control dictate a primary need for absolute orientation coding, whereas those of perception dictate a need for more categorical coding.

Notes: Abstract  In 12 subjects, each sitting on an armchair with the right forearm prone, the H-reflex elicited in the resting flexor carpi radialis muscle underwent cyclic excitability changes correlated with rhythmic flexion-extension movements of the ipsilateral foot (frequency of oscillations between 1.5 and 2.5 Hz). During foot plantar flexion, the H-reflex underwent a clear-cut increase, the maximum facilitation falling, in most subjects, within the second half of that phase; then, a gradual reduction in size led the reflex amplitude back to the initial value at the end of foot dorsal extension. If present also when the wrist and the ankle are moved together, this facilitation should favour the in-phase (isodirectional) association between movements and, conversely, hinder the anti-phase coupling.

Notes: Abstract  The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1–6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10–15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movementsinvolving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1–3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently.

Notes: Abstract  Interactions between proprioceptive and vestibular inputs contributing to the generation of balance corrections may vary across muscles depending on the availability of sensory information at centres initiating and modulating muscle synergies, and the efficacy with which the muscle action can prevent a fall. Information which is not available from one sensory system may be obtained by switching to another. Alternatively, interactions between sensory systems and the muscle to which this interaction is targeted may be fixed during neural development and not switchable. To investigate these different concepts, balance corrections with three different sets of proprioceptive trigger signals were examined under eyes-open and eyes-closed conditions in the muscles of normal subjects and compared with those of subjects with bilateral peripheral vestibular loss. The different sets of early proprioceptive inputs were obtained by employing three combinations of support surface rotation and translation, for which ankle inputs were nulled, normal or enhanced, the knees were either locked or in flexion, and the trunk was either in flexion or extension. Three types of proprioceptive and vestibulospinal interactions were identified in muscles responses. These interactions were typified by the responses of triceps surae, quadriceps, and paraspinal muscles. The amplitudes of stretch responses at 50 ms after the onset of ankle flexion in triceps surae muscles were related to the velocity of ankle stretch. The amplitude of balance-correcting responses at 100 ms corresponded more with stretch of the biarticular gastrocnemius when the knee was re-extended at 60 ms. Absent stretch reflexes at 50 ms in triceps surae with nulled ankle inputs caused a minor, 12-ms delay in the onset of balance-correcting responses in triceps surae muscles. Vestibular loss caused no change in the amplitude of balance-correcting responses, but a negligible decrease in onset latency in triceps surae even with nulled ankle inputs. Stretch responses in quadriceps at 80 ms increased with the velocity of knee flexion but were overall lower in amplitude in vestibular loss subjects. Balance-correcting responses in quadriceps had amplitudes which were related to the directions of initial trunk movements, were still present when knee inputs were negligible and were also altered after vestibular loss. Stretch and unloading responses in paraspinals at 80 ms were consistent with the direction of initial trunk flexion and extension. Subsequent balance-correcting responses in paraspinals were delayed 20 ms in onset and altered in amplitude by vestibular loss. The changes in the amplitudes of ankle (tibialis anterior), knee (quadriceps) and trunk (paraspinal) muscle responses with vestibular loss affected the amplitudes and timing of trunk angular velocities, requiring increased stabilizing tibialis anterior, paraspinal and trapezius responses post 240 ms as these subjects attempted to remain upright. The results suggest that trunk inputs provide an ideal candidate for triggering balance corrections as these would still be present when vestibular, ankle and knee inputs are absent. The disparity between the amplitudes of stretch reflex and automatic balance-correcting responses in triceps surae and the insignificant alteration in the timing of balance-correcting responses in these muscles with nulled ankle inputs indicates that ankle inputs do not trigger balance corrections. Furthermore, modulation of balance corrections normally performed by vestibular inputs in some but not all muscles is not achieved by switching to another sensory system on vestibular loss. We postulate that a confluence of trunk and upper-leg proprioceptive input establishes the basic timing of automatic, triggered balance corrections which is then preferentially weighted by vestibular modulation in muscles that prevent falling. The organisation of balance corrections around trunk inputs portrayed here would have considerable advantage for the infant learning balance control, but forces balance control centres to rely on limited sensory information related to this most unstable body segment, the trunk, when triggering balance corrections.

Notes: Abstract  Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after peripheral nerve injury. Therefore, one possible contributing factor of sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting in the DRG after peripheral nerve injury. The present study compared the extent of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in three rat neuropathic pain models: (1) the chronic constriction injury model (CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the segmental spinal nerve ligation injury model (SSI). All three methods of peripheral nerve injury produced behavioral signs of ongoing and evoked pain with some differences in the magnitude of each pain component. The density of sympathetic fibers in the DRG was significantly higher at all examined postoperative times than controls in the SSI model, while it was somewhat higher than controls only at the last examined postoperative time (20 weeks) in the CCI and PSI models. Therefore, data suggest that, although sympathetic changes in the DRG may contribute to neuropathic pain syndromes in the SSI model, other mechanisms seem to be more important in the CCI and PSI models at early times following peripheral nerve injury.

Notes: Abstract  The reaction times of saccades (SRT) to a suddenly presented visual stimulus (pro-saccade) can be decreased and a separate mode of express saccades can occur when a gap paradigm is used (i.e. fixation-point offset precedes target onset by 200 ms). A valid peripheral cue, presented briefly (100 ms) before target onset, has been found to facilitate the generation of saccades to the target, thereby increasing the frequency of express saccades and decreasing the mean latency. This facilitation occurs only for cues that correctly indicate the direction of the subsequent target presentation (valid cues). The present study investigates the effects of valid cues on SRTs and error rate in the anti-saccade task (saccades in the direction opposite to the stimulus) by systematically varying the cue lead time (CLT) and using the gap and overlap conditions, i.e. fixation point remains on throughout the trial. For a CLT of 100 ms, both reaction times and error rates were significantly increased. With increasing CLT (200–500 ms), both the reaction times of the anti-saccades and the error rates returned to approximately control level, with CLT more than 200 ms in both the gap and the overlap condition. Additional experiments using non-informative cues in the overlap task showed that the reaction times of correct anti-saccades and the error rate were decreased when cue and stimulus appeared at the same side. Analysis of the erratic pro-saccades revealed that almost all of them were corrected, i.e. they were followed by a second saccade towards the required location. It is found that the correction times were usually very short, with intersaccadic intervals between 0 and 150 ms. We suggest that the orienting mechanism, elicited by a transient peripheral cue, relates to the command and the decision to make a pro- rather than an anti-saccade. The cue elicits pro-orienting towards its position when a pro-saccade is required, and anti-orienting when an anti-saccade is required. The orienting effect is transient and decays with CLTs of more than 200 ms; this result holds for both anti-saccades and pro-saccades. Since subjects reported that they could not prevent the erratic pro-saccades or were often not aware of them, we conclude that this orienting mechanism occurs automatically, beyond voluntary control.

Notes: Abstract  Proprioceptive input arising from torsional body movements elicits small reflexive eye movements. The functional relevance of these eye movements is still unknown so far. We evaluated their slow components as a function of stimulus frequency and velocity. The horizontal eye movements of seven adult subjects were recorded using an infrared device, while horizontal rotations were applied at three segmental levels of the body [i.e., between head and shoulders (neck stimulus), shoulders and pelvis (trunk stimulus), and pelvis and feet (leg stimulus)]. The following results were obtained: (1) Sinusoidal leg stimulation evoked an eye response with the slow component in the direction of the movement of the feet, while the response to trunk and neck stimulation was oriented in the opposite direction (i.e., in that of the head). (2) In contrast, the gain behavior of all three responses was similar, with very low gain at mid- to high frequencies (tested up to 0.4 Hz) but increasing gain at low frequencies (down to 0.0125 Hz). We show that this gain behavior is mainly due to a gain nonlinearity for low angular velocities. (3) The responses were compatible with linear summation when an interaction series was tested in which the leg stimulus was combined with a vestibular stimulus. (4) There was good correspondence of the median gain curves when eye responses were compared with psychophysical responses (perceived body rotation in space; additionally recorded in the interaction series). However, correlation of gain values on a single-trial basis was poor. (5) During transient neck stimulation (smoothed position ramp), the neck response noticeably consisted of two components – an initial head-directed eye shift (phasic component) followed by a shift in the opposite direction (compensatory tonic component). Both leg and neck responses can be described by one simple, dynamic model. In the model the proprioceptive input is fed into the gaze network via two pathways which differ in their dynamics and directional sign. The model simulates either leg or neck responses by selecting an appropriate weight for the gain of one of the pathways (phasic component). The interaction results can also be simulated when a vestibular path is added. This model has similarities to one we recently proposed for human self-motion perception and postural control. A major difference, though, is that the proprioceptive input to the gaze-stabilizing network is weak (restricted to low velocities), unlike that used for perception and postural control. We hold that the former undergoes involution during ontogenesis, as subjects depend on the functionally more appropriate vestibulo-ocular reflex. Yet, the weak proprioceptive eye responses that remain may have some functional relevance. Their tonic component tends to stabilize the eyes by slowly shifting them toward the primary head position relative to the body support. This applies solely to the earth-horizontal plane in which the vestibular signal has no static sensitivity.

Notes: Abstract  Disparities in load stiffness were used to differentiate and characterize pinch-force, finger-span, and pinch-effort matching in two experiments. All subjects squeezed a spring-loaded manipulandum in each hand using three-finger pinch. Subjects in the first experiment were instructed explicitly to match one of the three continua. Subjects matching force or span were told to attend carefully to sensations from the hand or arm and to ignore differences in the effort required to make the sensations equal. They had to achieve and hold a particular target force with the reference hand and then match force or span with the opposite hand, usually against a spring with a different stiffness. These subjects were given as much time as necessary to make their matches and were told which hand was serving as the reference in each trial. Effort-matching subjects were told to ignore peripheral sensations and to match effort or motor commands. These subjects were not told which hand was the reference and were given only 1 s to make a match, so they made matches by rapidly squeezing both manipulanda simultaneously and, presumably, with the same voluntary motor command. The matching behaviors of the three groups were clearly distinguishable and were consistent with instructions. Results were similar whether different subjects were assigned different instructions or the same subjects performed all three match types. In a second experiment, naïve subjects were given purposely ambiguous instructions without reference to a specific continuum and had no time or accuracy constraints. Subjects produced the same three sensorimotor behaviors obtained with explicit instructions, showing that the different behaviors were not artifacts of strict protocols. Taken together, the results show that force, span, and effort are distinct sensorimotor continua that can be judged reliably.

Notes: Abstract  We investigated force-sharing among three fingers which acted in parallel and produced ramp profiles of total force from zero to the maximal voluntary force. The feedback to the subject was provided by a visual signal on the monitor and could correspond to the sum of forces of all the fingers or to the sum of forces of two fingers, while the force of the third finger was added with a coefficient 2 or 0.5. If the subjects did not know about the distorted feedback, they showed a template-sharing pattern within the whole range of total force values. This pattern did not depend on which finger force was multiplied and by which coefficient. If the subjects knew in advance how the feedback signal would be calculated, they tried to perform the task using either only the finger whose force was multiplied by 2 or two fingers when the force of the third one was multiplied by 0.5. Further into the trial, however, they were unable to track the ramp pattern using only one or two fingers and demonstrated a search activity that could continue until the end of the trial or lead eventually to a three-finger sharing pattern similar to the template pattern used in cases of undistorted feedback. We conclude that the limited number of preferred sharing pattern within the studied task reflects an organization of the fingers into a structural unit (involving one, two, or all three fingers) by the central nervous system. The availability of structural units defines the presence of stable solutions available for the system.

Notes: Abstract  The role played by the attentional mechanisms that enable dominance of relevant objects over distractor objects was investigated by measuring changes in the kinematics of the reach-to-grasp movement. Subjects reached towards three-dimensional (3D) stimuli while attention was diverted towards distracting information consisting of either two-dimensional (2D) projected shapes or 3D objects. Movement kinematics were influenced to a greater degree when a secondary task was performed involving a 3D object rather than a 2D projected shape. When the distractor was 3D, both the reaching and the grasping components were altered but, when it was 2D only, the reaching component was modified. It is suggested that, when attention is directed towards a distractor, it is associated with interference in the kinematics of the action towards the target. Further, the nature and dimensions of the distractor selectively influence the reach or the grasp component of a prehension movement.

Notes: Abstract  We studied the changes in the anticipatory postural adjustments (APAs), associated with dropping a load from extended arms and during fast bilateral shoulder flexion movements, when movements were performed in a self-paced manner and under a simple reaction-time instruction. The latter instruction applied time pressure and did not allow the regular pattern of APAs to be used. In particular, the following questions were asked: (1) are there changes in the relative timing of APAs under the reaction time condition; (2) are changes in the relative timing of APAs associated with changes in APAs themselves; (3) can different postural strategies be used to maintain stability under self-paced and reaction time conditions; and (4) are changes in APAs related to actual reaction time or to a change in the instruction? In particular, under reaction-time conditions, APAs occurred later in time, typically simultaneously with the initiation of the focal movement. Additional changes in electromyographic (EMG) patterns in postural muscles included an increase in the amplitude of EMG bursts and “speeding-up” some of the tri-phasic patterns in postural dorsal-ventral muscle pairs. This was accompanied by a smaller early shift of the center of pressure followed by its more rapid delayed displacement. There was considerable variability in the changes of EMG and dynamic characteristics across subjects. Some of the changes in the EMG patterns in postural muscles depended on actual reaction time, while others were related to a change in the instruction and occurred even if actual reaction times were long enough to allow for the typical self-paced APA patterns to occur. These findings can be interpreted as supporting the parallel control hypothesis for the focal movement and postural adjustments. Alternatively, they can be interpreted within a framework that implies the generation of a single control function, which is transformed into two components, one directed at the focal muscles/joints and the other directed at postural muscles/joints.

Notes: Abstract  This purpose of this study was to examine the spatial coding of eye movements during static roll tilt (up to ±45°) relative to perceived earth and head orientations. Binocular videographic recordings obtained in darkness from eight subjects allowed us to quantify the mean deviations in gaze trajectories along both horizontal and vertical coordinates relative to the true earth and head orientations. We found that both variability and curvature of gaze trajectories increased with roll tilt. The trajectories of eye movements made along the perceived earth-horizontal (PEH) were more accurate than movements along the perceived head-horizontal (PHH). The trajectories of both PEH and PHH saccades tended to deviate in the same direction as the head tilt. The deviations in gaze trajectories along the perceived earth-vertical (PEV) and perceived head-vertical (PHV) were both similar to the PHH orientation, except that saccades along the PEV deviated in the opposite direction relative to the head tilt. The magnitude of deviations along the PEV, PHH, and PHV corresponded to perceptual overestimations of roll tilt obtained from verbal reports. Both PEV gaze trajectories and perceptual estimates of tilt orientation were different following clockwise rather than counterclockwise tilt rotation; however, the PEH gaze trajectories were less affected by the direction of tilt rotation. Our results suggest that errors in gaze trajectories along PEV and perceived head orientations increase during roll tilt in a similar way to perceptual errors of tilt orientation. Although PEH and PEV gaze trajectories became nonorthogonal during roll tilt, we conclude that the spatial coding of eye movements during roll tilt is overall more accurate for the perceived earth reference frame than for the perceived head reference frame.

Notes: Abstract  It is still not clear whether the transition from pursuit eye movements to fixation is mediated by the same system that initiates pursuit, or whether another system, a specialized fixation system, is responsible. To investigate this question we measured smooth-pursuit eye movements and smooth-pursuit termination in five normal subjects using both predictable and unpredictable step-ramp stimuli (velocities 10° and 20°/s) in front of a homogeneous and a structured visual background in order to compare the profile of eye velocity under these different conditions. With the predictable and/or structured visual background there was a gradual transition of eye velocity toward zero. In contrast, with the unpredictable stimulus in front of a homogeneous background, eye velocity during the offset was characterized by an overshoot (on the average, 2.2±1.0°/s for 10°/s ramps) before eye velocity settled at zero. Under this condition, steady-state velocity gain and the deceleration of the offset were significantly higher than during the other paradigm with the same target velocity. The latency of the pursuit offset was significantly shorter when a predictable stimulus was used. The duration of the offset did not depend on the experimental condition used. These findings imply that the pursuit onset and offset have some similarities and may be mediated by the same oculomotor system.

Notes: Abstract  Memory for object-place configurations appears to be a common function of the hippocampus in the human and monkey brain. The nature of the spatial information which enters into these object-configural memories in the primate, and the location of the memories themselves, have remained obscure, however. In the rat, much evidence indicates that the hippocampus processes idiothetic spatial information, an estimate of the animal’s current environmental location derived from path integration. I propose that in primates the hippocampus provides idiothetic information about the environmental location of body parts, and that the main function of this information in the primate brain is to become configured with object-identity information provided by temporal lobe cortex outside the hippocampus.

Notes: Abstract Objectives: Calcium may be indicated in critically ill patients for hemodynamic support. Its well-known action includes peripheral vasoconstriction. Vascular effects of calcium are unknown, however, in the presence of hypertension or in combination with calcium channel blocking drugs, commonly prescribed in the treatment of hypertension. The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitable study model, because their vascular reactivity closely agrees with that in hypertensive humans. The present study should clarify (a) are the renal vessels of SHR responsive to high and low ionized calcium ([Ca++] within the clinical ranges? (b) because release of nitric oxide is calcium ion dependent, are renal vascular responses altered after inhibition of NO synthase? (c) are vascular responses of SHR to hypercalcemia altered by the calcium channel blocking drug verapamil? Animals and interventions: We compared isolated kidneys of SHR and those of two strains of age-matched normotensive rats (NTR) in their responses to high and low [Ca++]. They were perfused with oxygenated, warmed (37 °C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady state high [Ca++] (1.88 mmol/l) and low [Ca++] (0.55 mmol/l) were instituted in randomized order. In protocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with NG monomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca++] levels were instituted in SHR after verapamil pretreatment. At each [Ca++] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mm Hg. Results: In SHR (perfusion pressure 100 mm Hg), high [Ca++] induced a decrease in renal flow (–11.8 ± 1.8 % of control), which was significantly greater (p 〈 0.05) than the change (− 6.1 ± 1.5 and − 6.9 ± 1.4 % of control) recorded in the two normotensive strains. In SHR (perfusion pressure 150 mmHg), high [Ca++] induced a decrease in renal flow (− 12 ± 1.3 % of control), also significantly greater (p 〈 0.05) than the changes (− 6.2 ± 1.1 and −5.8 ± 1.7 % of control) in the two normotensive strains. Similar differences and significances were again observed after L-NMMA pretreatment. In SHR, verapamil prevented renal vascular responses in SHR to both high and low [Ca++]. Conclusions: First, renal vascular responses to high [Ca++] in SHR are exaggerated. At the upper end of the hypercalcemia range the observed changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticipated to be even less pronounced. Second, effects of high [Ca++] were abolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hypertension.

Notes: Abstract  The effects of 14 days of space flight on the glucose transporter protein (GLUT-4) were studied in the plantaris muscle of growing 9-week-old, male Sprague Dawley rats. The rats were randomly separated into five groups: pre-flight vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch; flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after the return from space; and synchronous ground controls (SC-R0 and SC-R9) sacrificed at the same time as the respective flight groups. The flight groups F-R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module located in the cargo bay of the shuttle transport system – 58 of the manned Space Shuttle for the NASA mission named ”Spacelab Life Sciences 2”. Body weight and plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC. Neither body weight nor plantaris muscle weight in either group had changed 9 days after the return from space. As a result, body weight and plantaris muscle weight did not differ between the flight and synchronous control groups at any of the time points investigated. The GLUT-4 content (cpm/µg membrane protein) in the plantaris muscle did not show any significant change in response to 14 days of space flight or 9 days after return. Similarly, citrate synthase activity did not change during the course of the space flight or the recovery period. These results suggest that 14 days of space flight does not affect muscle mass or GLUT-4 content of the fast-twitch plantaris muscle in the rat.