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PubMed1981

Hexacarbon neurotoxicity.

The neurotoxicity of hexacarbon solvents has become apparent only recently, but an extensive literature has already developed as a result of the clinical and epidemiological implications of the human disease, and the advantages of small animal models of hexacarbon neurotoxicity in investigation of experimental neuropathies. This review selectively summarizes the literature, focusing on clinical manifestations and pathological alterations in the peripheral nerves. The clinical manifestations are dominated by a distal, symmetrical, sensorimotor polyneuropathy. Pathological changes include distal axonal degeneration and formation of neurofilament-filled axonal swellings in early or moderately severe exposure. A late manifestation in severely affected experimental animals is recurrent demyelination and remyelination.

Adolescent↗
PubMed2001

Learning to communicate.

Of the few animal groups that learn their vocalizations, songbirds are uniquely amenable to molecular, physiological, and behavioral analyses of the neural features responsible for vocal learning. In order to communicate effectively as an adult, a young songbird recognizes and memorizes a model of his species-specific song during a developmentally critical period called sensory acquisition. Factors are now emerging that contribute to the length and strength of this learning phase. In a second critical period, known as sensorimotor learning, the young bird uses auditory feedback to perfect his motor performance, creating a match to the memorized model. New studies show that motor matching can persist beyond sensorimotor learning, and thus a role for the acquired model might also persist into adulthood. Fascinating in their own right, songbirds also provide optimism that mature brains have recourse to plasticity.

Animals↗
PubMed1995

Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors.

Vigilance, anxiety, epileptic activity, and muscle tone can be modulated by drugs acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABAA) receptors. In vivo, BZ sites are potential targets for endogenous ligands regulating the corresponding central nervous system states. To assess the physiological relevance of BZ sites, mice were generated containing GABAA receptors devoid of BZ sites. Following targeted disruption of the gamma 2 subunit gene, 94% of the BZ sites were absent in brain of neonatal mice, while the number of GABA sites was only slightly reduced. Except for the gamma 2 subunit, the level of expression and the regional and cellular distribution of the major GABAA receptor subunits were unaltered. The single channel main conductance level and the Hill coefficient were reduced to values consistent with recombinant GABAA receptors composed of alpha and beta subunits. The GABA response was potentiated by pentobarbital but not by flunitrazepam. Diazepam was inactive behaviorally. Thus, the gamma 2 subunit is dispensable for the assembly of functional GABAA receptors but is required for normal channel conductance and the formation of BZ sites in vivo. BZ sites are not essential for embryonic development, as suggested by the normal body weight and histology of newborn mice. Postnatally, however, the reduced GABAA receptor function is associated with retarded growth, sensorimotor dysfunction, and drastically reduced life-span. The lack of postnatal GABAA receptor regulation by endogenous ligands of BZ sites might contribute to this phenotype.

Animals↗
PubMed1991

Motor deficits are produced by removing some cortical transplants grafted into injured sensorimotor cortex of neonatal rats.

Fetal frontal cortex was transplanted into cavities formed in the right motor cortex of neonatal rats. As adults, the animals were trained to press two levers in rapid succession with their left forelimb to receive food rewards. Once they had reached an optimal level of performance, the effect of removing their transplants was assessed. Surgical removal of transplants significantly impaired the performance of 2 of 4 subjects. Placing a cross-strain skin graft to induce the immunological rejection of the transplants produced a behavioral deficit in 1 of 2 subjects with complete transplant removal. Skin grafts produced no behavioral effects in four subjects that had surviving transplants. Since the motor deficits produced by transplant removal resembled those observed following the removal of normal motor cortex, we propose that these three transplants functioned within the host brain. Histology showed that the procedures used to remove cortical grafts did not injure any host brains. Therefore, host brain damage is unlikely to account for the behavioral deterioration that followed transplant removals.

Animals↗
PubMed2002

Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study.

The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region-specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin.

Adolescent↗
PubMed2006

Longitudinal studies of antisaccades in antipsychotic-naive first-episode schizophrenia.

BACKGROUND: Prefrontal cortical dysfunctions, including disturbances in adaptive context-specific behavior, have been reported in neuropsychological and brain imaging studies of schizophrenia. Some data suggest that treatment with antipsychotic medications may ameliorate these deficits. METHOD: We investigated antisaccade performance in 39 antipsychotic-naive, first-episode schizophrenia patients who were re-evaluated 6 weeks after treatment initiation. A group of matched healthy subjects were examined at similar time-points. Patients and healthy individuals available for longer-term testing were re-assessed 26 and 52 weeks after initial testing. RESULTS: Before treatment, patients showed elevated rates of response suppression errors and prolonged latencies of correct antisaccades. Increased rates of antisaccade errors were associated with faster response latencies during a separate, visually guided saccade task, but only prior to treatment. Throughout the 1-year follow-up, patients progressively improved in their ability to voluntarily suppress context-inappropriate behavior. Although treatment assignment was by clinician choice, results of exploratory analyses revealed that patients treated with risperidone progressively planned and initiated correct antisaccades more quickly than patients receiving haloperidol. CONCLUSIONS: Deficits in the voluntary control of spatial attention are exaggerated during acute episodes of illness, but remain an enduring aspect of prefrontal dysfunction in schizophrenia even after treatment. During acute illness, speeded sensorimotor transformations may compound these deficits and contribute to the heightened distractibility associated with acute psychosis. Continued improvement in task performance throughout the 1-year follow-up suggests that partial normalization of prefrontal cognitive functions resulting from antipsychotic treatment may have a longer and more gradual time course than the reduction of acute psychotic symptoms.

Adolescent↗
PubMed1980

Physiological and behavioral changes produced by cerebellar stimulation in the monkey.

Small surface electrodes were placed bilaterally over the intermediate or lateral cerebellar cortex of cynomolgus monkeys to determine how electrical stimulation of different areas of the cerebellar cortex affected average evoked responses and a sequential forelimb movement. Biphase electrical stimulation was applied between various electrode combinations, and various intensities and frequencies were established for each combination. Transcortical stimulation between the right and left intermediate cerebellar cortex required the lowest intensity (1.5 microC/sq cm/ph) to elicit an average evoked response in the sensorimotor cortex; stimulation between the electrodes over the contralateral intermediate or lateral cortex required slightly higher levels (2.0 microC/sq cm/ph). No response could be elicited from stimulating the ipsilateral cortex. Likewise, 1 minute of transcortical stimulation was more effective than comparable stimulation of the contralateral intermediate or lateral cortex in altering the waveforms of a somatosensory evoked response. Transcortical stimulation also modified the forelimb movement, whereas contralateral stimulation of the intermediate or lateral cortex had little or no effect. Transcortical stimulation at 2.0 microC/sq cm/ph, with frequencies of 150 Hz or higher, increased the time required to execute the forelimb movement but did not affect the accuracy of the movement. High-speed motion pictures indicated that transcortical stimulation decreased the velocity of forelimb movement and in some cases also affected the limb trajectory. These results indicate that consideration should be given to the area of the cerebellum stimulated and to the mode of stimulation, in the hope of achieving optimum clinical benefit.

Animals↗
PubMed1998

Acoustic startle, prepulse inhibition, locomotion, and latent inhibition in the neuroleptic-responsive (NR) and neuroleptic-nonresponsive (NNR) lines of mice.

The acoustic startle reflex (ASR) is inhibited by low intensity acoustic stimuli (prepulse inhibition; PPI) delivered prior to the startle stimulus. PPI may reflect underlying sensorimotor processes involved in the filtering of exteroceptive stimuli for their cognitive or physiological relevance. Latent inhibition (LI) is a cognitive process in which pre-exposure to the conditioned stimulus (CS) produces pro-active interference with the acquisition of an associative learning task. LI is thought to reflect a selective attention mechanism that contributes to an organism's ability to adjust its behavior to changing contingencies of reinforcement. In the present series of experiments, the ASR, PPI at three prepulse intensities (56, 68, and 80 dB), locomotor activity, and LI using an active avoidance paradigm were assessed in mice bidirectionally selected from a heterogeneous stock for response (NR line) or nonresponse (NNR line) to neuroleptic-induced catalepsy. A randomly selected line was used as the control. Mice from the NNR line displayed weak startle responses and a complete absence of PPI. In contrast, the NR line displayed the largest ASR and the greatest PPI. The control line displayed ASRs and PPI values intermediate to the selected lines. Locomotor activity which is known to affect LI was lowest in the NR line but was similar in the NNR and control lines. In the LI paradigm, acquisition of the avoidance response was impaired in mice from the NR and control lines that were pre-exposed to the auditory CS (normal response). In contrast, the acquisition of the avoidance response in the NNR line was similar in CS pre-exposed and CS non-pre-exposed animals. Overall, the results demonstrate that some of the same genetic factors which regulate neuroleptic response also play a significant role in PPI and LI.

Acoustic Stimulation↗
PubMed1987

The organization of the nucleus basalis-neostriatum complex of the mallard (Anas platyrhynchos L.) and its connections with the archistriatum and the paleostriatum complex.

The pattern of connections between the nucleus basalis, neostriatum, hyperstriatum ventrale, paleostriatum complex and archistriatum in the mallard has been analysed using Nissl material and a combination of neuroanatomical tracing procedures (autoradiography, horseradish peroxidase and horseradish peroxidase-wheat germ agglutinin histochemistry, lesion/degeneration technique). The frontal part of the mallard's telencephalon is characterized by its multilayered organization and the predominantly vertical arrangement of the connecting fiber systems. The nucleus basalis, endstation of the ascending sensory trigeminal system, is a large laminar cell area with a dorsal and a ventral layer. The overlying neostriatum frontale can be subdivided into a medial, a dorsal and a ventral intermediate, and a lateral area. The nucleus basalis has distinct connections with the ventral layer and sparse connections with the dorsal layer of the intermediate neostriatum, and abundant reciprocal connections with the ventral layer of the hyperstriatum ventrale. The ventral intermediate neostriatum also has reciprocal connections with the hyperstriatum ventrale; its projections overlap partly with those from the nucleus basalis. The ventral layer of the intermediate neostriatum frontale has a distinct projection upon the paleostriatum augmentatum. The dorsal layer sends fibers to the lateral neostriatum, to the rostral "sensorimotor" part of the archistriatum and to the lateral zone of the lobus parolfactorius. Another source of archistriatal afferents is the paleostriatum ventrale, an area that may also send fibers to the brainstem. Figure 21 summarizes the connections described in this paper. The functional significance of this organization is discussed in relation to its possible role in the guidance of pecking and other feeding behaviors in the mallard. Differences in the organization of the systems in pigeon and mallard are related to the differing degrees of visual and tactile (trigeminal) contributions to feeding in the two birds. It is suggested that the pattern of reciprocal connections between the hyperstriatum ventrale and the nucleus basalis and ventral intermediate neostriatum frontale forms the neuroanatomical substrate for a "comparator-system".

Animals↗
PubMed1994

Tropism and corticospinal target selection in the rat.

Layer V pyramidal cells in the intermediate part of the cerebral cortex enter the lumbar spinal gray, but not the cervical spinal gray matter, during the first postnatal week. To study if the ingrowth of intermediate corticospinal axons into the lumbar spinal gray is guided by a diffusible tropic factor, we co-cultured explants of the intermediate part of the sensorimotor cortex and of the lumbar spinal gray matter in 3-D collagen gels. Using this test system, a target specific directional growth of cortical axons towards the lumbar spinal gray explant can be demonstrated in vitro. Retrograde labeling indicates that most labeled cell bodies were located in layer V of the cortex explant and were characterized by a pyramidal cell shape. Furthermore, axon behavior of retrogradely labeled neurons within the cortical explant is considerably affected by the presence of lumbar spinal gray target tissue. In contrast to lumbar spinal gray innervation, intermediate corticospinal tract axons do not enter the cervical spinal gray in vivo. Is it the inability of intermediate corticospinal tract axons to respond to cervical target-derived influences? In the current study we co-cultured explants of the intermediate cortex and cervical spinal gray matter in 3-D collagen gels. Our data indicate that in vitro axons from layer V neurons in the intermediate part of the cortex are capable of recognizing and responding to a diffusible factor released by the cervical spinal cord target area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Increased responses to adenosine and 2-chloroadenosine of cyclic AMP-generating systems in the primary cortical region of cobalt-induced epilepsy in the rat.

The epileptic activity was induced by an injection of cobalt chloride solution into the unilateral sensorimotor cortex of rats. Cyclic AMP accumulations elicited by adenosine and 2-chloroadenosine were investigated in slices from different regions of the epileptic cortex. The cyclic AMP accumulation was increased in the primary cortical region of cobalt-induced epilepsy. The greatest increase in cyclic AMP accumulation was detected between 2 and 3 weeks after treatment by cobalt, in conjunction with the electrographic and behavioral findings. The results suggest the functional significance of cortical cyclic AMP-generating systems in cobalt-induced epilepsy.

2-Chloroadenosine↗
PubMed2004

Relationship of tyrosine hydroxylase and serotonin immunoreactivity to sensorimotor circuitry in larval zebrafish.

Our previous study tracked the ontogeny of aminergic systems in zebrafish (Danio rerio). Here we use tyrosine hydroxylase (TH) and serotonin (5-hydroxytryptamine; 5-HT) immunoreactivity, in conjunction with retrograde and genetic labeling techniques, to provide a more refined examination of the potential synaptic contacts of aminergic systems. Our focus was on different levels of the sensorimotor circuit for escape, from sensory inputs, through identified descending pathways, to motor output. We observed 5-HT reactivity in close proximity to the collaterals of the Rohon-Beard sensory neurons in spinal cord. In the brainstem we found TH and 5-HT reactivity closely apposed to the dendritic processes of the nucleus of the medial longitudinal fascicle (nMLF), in addition to the ventral dendrites of the Mauthner neuron and its serial homologs MiD2cm and MiD3cm. Only TH reactivity was observed near the lateral dendrites of the Mauthner cell. TH and 5-HT reactivity were also positioned near the outputs of reticulospinal cells in spinal cord. Finally, both TH and 5-HT reactivity were detected close to the dendritic processes of primary and secondary spinal motor neurons. We also confirmed, using dual TH and 5-HT staining and retrograde labeling, that the sources of spinal aminergic reactivity include the posterior tuberculum (dopamine) and inferior raphe region (5-HT). Our data indicate that aminergic systems may interact at all levels of the sensorimotor pathways involved in escape. The identification of some of these likely sites of aminergic action will allow for directed studies of their functional roles using the powerful combination of techniques available in zebrafish.

Afferent Pathways↗
PubMed1992

Sensorimotor and cognitive consequences of middle cerebral artery occlusion in rats.

Rats were subjected to either right proximal middle cerebral artery (MCA) occlusion or sham operation, and examined for an extended period on a battery of tests designed to measure simple motor function, sensorimotor integration and cognitive function. Rats with MCA occlusion showed extensive neuronal loss in the dorsolateral striatum and variable neuron loss in the parietal, temporal and frontolateral neocortex. MCA occluded animals exhibited significant impairments in tests of postural reflex, visual and tactile forelimb placing, locomotor coordination, and a test of simultaneous bilateral tactile extinction. The reflex and sensorimotor function deficits recovered to pre-operative levels by Day 30 post-ischemia. Five weeks following surgery, rats were tested in 2 versions of the Morris water task. Rats with MCA occlusion demonstrated significant impairments in their ability to navigate to a hidden platform, but were not significantly impaired on the visible (cued) version of the task. This general pattern of transient sensorimotor and reflex deficits, but with more persistent cognitive impairments, is similar to that seen in humans following MCA infarcts.

Animals↗
PubMedDate not supplied

[Intercentral reticulo-cortical relations of brain electrical activity during "animal hypnosis" in rabbits].

The electrical activity of the right and left sensorimotor and premotor cortical areas and right and left medulary reticular formation was recorded during "animal hypnosis" in rabbits. In this state, the spectral power of potentials (predominantly, in the delta-range) recorded from the left reticular formation was higher than that recorded from the right side. The value of the function of coherence between the right and left reticular recordings was decreased to 0.1-0.2 in the whole frequency range. The tight-side intrahemispheric coherence between the activities recorded from the sensorimotor cortex and reticular formation was higher than respective left-side values, whereas the coherent relations between the activities recorded from the reticular formation and premotor cortex were not changed (as compared to nonhypnotic state).

Animals↗
PubMed2004

Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans.

A landmark of corticostriatal connectivity in nonhuman primates is that cortical connections are organized into a set of discrete circuits. Each circuit is assumed to perform distinct behavioral functions. In animals, most connectivity studies are performed using invasive tracing methods, which are nonapplicable in humans. To test the proposal that corticostriatal connections are organized as multiple circuits in humans, we used diffusion tensor imaging axonal tracking, a new magnetic resonance technique that allows demonstration of fiber tracts in a noninvasive manner. Diffusion tensor imaging-based fiber tracking showed that the posterior (sensorimotor), anterior (associative), and ventral (limbic) compartments of the human striatum have specific connections with the cortex, and particularly the frontal lobes. These results provide the first direct demonstration of distinct corticostriatal connections in humans.

Adult↗
PubMed2004

Unilateral ischemic sensorimotor cortical damage induces contralesional synaptogenesis and enhances skilled reaching with the ipsilateral forelimb in adult male rats.

Unilateral damage to the forelimb representation area of the sensorimotor cortex (SMC) results in a compensatory reliance on the unimpaired (ipsilateral to the lesion) forelimb as well as reorganization of neuronal structure and connectivity in the contralateral motor cortex. Recently, male rats with unilateral electrolytic SMC lesions were found to have enhanced skilled reaching performance with the ipsilesional forelimb compared with sham-operated controls. The present study was performed to determine whether these behavioral findings are replicable using an ischemic lesion and whether there is a link between the enhanced learning and synaptogenesis in motor cortical layer V opposite the trained limb and lesion, as assessed using stereological methods for light and electron microscopy. Rats were given a sham operation or an endothelin-1 (ET-1) induced ischemic SMC lesion. They were then trained for 20 days on a skilled reaching task with the unimpaired limb or received control procedures. As with previous findings using electrolytic lesions, rats with unilateral ischemic SMC lesions performed significantly better using the unimpaired forelimb than did sham-operates. Lesions, but not training, significantly increased the total number of motor cortical layer V synapses per neuron as well as the number of perforated and multisynaptic bouton (MSB) synapses per neuron compared with shams. Thus, in addition to a net increase in synapses, the improved reaching ability was coupled with an increase in synapse subtypes that have previously been linked to enhanced synaptic efficacy. The failure to induce synaptogenesis in layer V with reach training alone is in contrast to previous findings and may be related to training intensity.

Age Factors↗
PubMed1995

Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine.

Prepulse inhibition (PPI) of the startle reflex provides an operational measure of sensorimotor gating. Deficits in PPI are observed in schizophrenia patients and can be modelled in animals by administration of noncompetitive NMDA antagonists such as phencyclidine (PCP) or dizocilpine (MK-801). Previous studies indicate that the atypical antipsychotic clozapine restores PPI in PCP-treated animals while the typical antipsychotic haloperidol does not. Olanzapine (LY170053) is a novel putative atypical antipsychotic that shares many pharmacological and behavioral properties with clozapine. The present study assessed the ability of olanzapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg) to antagonize deficits in PPI produced by PCP (1.5 mg/kg) and dizocilpine (0.1 mg/kg). At the two highest doses, olanzapine significantly increased PPI in PCP- and dizocilpine-treated animals without affecting PPI or baseline startle reactivity by itself. These results support the notion that olanzapine is functionally similar to clozapine and may have utility as an atypical antipsychotic agent.

Acoustic Stimulation↗
PubMed2005

Species-specific differences in sensorimotor adaptation are correlated with differences in social structure.

Here, we report a species difference in the strength and duration of long-term sensorimotor adaptation in the electromotor output of weakly electric fish. The adaptation is produced by changes in intrinsic excitability in the electromotor pacemaker nucleus; this change is a form of memory that correlates with social structure. A weakly electric fish may be jammed by a similar electric organ discharge (EOD) frequency of another fish and prevents jamming by transiently raising its own emission frequency, a behavior called the jamming avoidance response (JAR). The JAR requires activation of NMDA receptors, and prolonged JAR performance results in long-term frequency elevation (LTFE) of a fish's EOD frequency for many hours after the jamming stimulus. We find that LTFE is stronger in a shoaling species (Eigenmannia virescens) with a higher probability of encountering jamming conspecifics, when compared to a solitary species (Apteronotus leptorhynchus). Additionally, LTFE persists in Eigenmannia, whereas, it decays over 5-9 h in Apteronotus.

Acclimatization↗