Chronic Administration of Quinolinic Acid in the Rat Striatum Causes Spatial Learning Deficits in a Radial Arm Water Maze Task

Chronic intrastriatal administration of quinolinic acid (QA) in the rat produces a pattern of neurodegeneration similar to that seen in Huntington's disease (HD). Although these changes have been related to transient motor abnormalities, the effects of chronic QA administration on cognitive abilities have not been assessed. The present study investigated whether the striatal deterioration observed during chronic QA administration produces cognitive impairments in this animal model of HD by testing the effects of chronic administration of QA on spatial learning ability of rats in a radial arm water maze (RAWM) task. Rats were given bilateral implantation of a chronic dialysis probe apparatus which delivered either vehicle or QA (20 mM) into the striatum. Beginning 1 day after implantation, the rats were tested daily for 3 weeks in the RAWM. Nocturnal activity levels were also assessed at 1-, 3-, 5-, 7-, 14-, and 21-days following probe implantation. Results of behavioral testing indicated that chronic exposure to QA causes spatial learning deficits in the RAWM task with only a transient increase in activity levels. Collectively, these results suggest that chronic striatal exposure to QA mimics some aspects of the cognitive deficits observed in HD.     

Age-Dependent Differences in Survival of Striatal Somatostatin–NPY–NADPH–Diaphorase-Containing Interneurons versus Striatal Projection Neurons after Intrastriatal Injection of Quinolinic Acid in Rats

Some authors have reported greater sparing of neurons containing somatostatin (SS)–neuropeptide Y (NPY)–NADPH-diaphorase (NADPHd) than projection neurons after intrastriatal injection of quinolinic acid (QA), an excitotoxin acting at NMDA receptors. Such findings have been used to support the NMDA receptor excitotoxin hypothesis of Huntington's disease (HD) and to claim that intrastriatal QA produces an animal model of HD. Other studies have, however, reported that SS/NPY/NADPHd interneurons are highly vulnerable to QA. We examined the influence of animal age (young versus mature), QA concentration (225 mMversus 50 mM), and injection speed (3 min versus 15 min) on the relative SS/NPY/NADPHd neuron survival in eight groups of rats that varied along these parameters to determine the basis of such prior discrepancies. Two weeks after QA injection, we analyzed the relative survival of neurons labeled by NADPHd histochemistry, SS/NPY immunohistochemistry, or cresyl violet staining (which stains all striatal neurons, the majority of which are projection neurons) in the so-called lesion transition zone (i.e., the zone of 40–60% neuronal survival). We found that age, and to a lesser extent injection speed, had a significant effect on relative SS/NPY/NADPHd interneuron survival. The NADPHd- and SS/NPY-labeled neurons typically survived better than projection neurons in young rats and more poorly in mature rats. This trend was greatly accentuated with fast QA injection. Age-related differences may be attributable to declines in projection neuron sensitivity to QA with age. Since rapid QA injections result in excitotoxin efflux, we interpret the effect of injection speed to suggest that brief exposure to a large dose of QA (with fast injection) may better accentuate the differential vulnerabilities of NADPHd/SS/NPY interneurons and projection neurons than does exposure to the same total amount of QA delivered more gradually (slow injection). These findings reconcile the discordant results found by previous authors and suggest that QA injected into rat striatum does reproduce the neurochemical traits of HD under some circumstances. These findings are consistent with a role of excitotoxicity in HD pathogenesis, and they also have implications for the basis of the more pernicious nature of striatal neuron loss in juvenile onset HD.     

Behavioral and electrophysiological correlates of the quinolinic acid rat model of Huntington's disease in rats

The influence of bilateral intrastriatal injection of quinolinic acid (QA, 300 nmol) was studied in male Wistar rats. Behavioral and electrophysiological experiments were conducted in 15 lesioned plus 15 vehicle-injected (control) animals. With respect to control animals, QA-lesioned rats showed marked, statistically significant alterations from both the behavioral (greater motor activation in response to d-amphetamine, place-learning deficit in the Morris water maze), and the electroencephalographic (reduced voltage amplitude and EEG power at the level of frontal cortex) points of view. In addition, a significant loss in body weight and a marked striatal gliosis (GFAP staining) were observed in lesioned rats. Conversely, QA-lesioned rats did not show modifications in posttetanic potentiation (P.T.P.) or long-term potentiation (L.T.P.) in CA1 hippocampal area. The present results confirm that QA lesions of rat striatum may be regarded as a suitable model of Huntington's disease (HD).     

Rolipram reduces excitotoxic neuronal damage

Proinflammatory cytokines are supposed to be involved in the pathophysiology of neuronal damage following excitotoxic lesions. We examined the effect of rolipram, a TNF-alpha-inhibitor, on excitotoxic neuronal damage. Quinolinic acid (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. Four groups of QA rats were treated i.p. with solvent, MK-801 (4 mg/kg) or rolipram (0.3 mg/kg) which was started either 6 or 24 h after QA injection and continued with daily applications for 14 days. QA injection induced neuronal damage which affected 93% of the striatal area. MK-801 reduced this damage to 12% of the striatal area. Treatment with rolipram when started at 6 h after QA injection resulted in neuronal damage amounting to 60%; the result after starting at 24 h was not different from solvent (91%). The present results demonstrate that rolipram reduces neuronal damage induced by intrastriatal QA application.     

Quinolinic acid released from polymeric brain implants causes behavioral and neuroanatomical alterations in a rodent model of Huntington's disease

Quinolinic acid (QA) is an N-methyl-d-aspartate agonist that has been shown to produce neurotoxic effects that mimic certain neurodegenerative diseases when administered to laboratory animals. Intrastriatal injections of QA in rats have been used extensively to produce some of the neuropathological and behavioral deficits that are analogous to Huntington's disease (HD). However, acute intrastriatal injections of QA produce symptoms that are not analogous to the progressive nature of HD. Thus far, models using chronic administration of QA that produce HD-like behavioral and neuroanatomical changes have necessitated the use of a relatively bulky and fragile microdialytic pump apparatus. The present study tested an alternative way of chronically administering QA. Specifically, this study tested whether gradual release of QA from ethylene vinylacetate (EVA) polymers could produce symptoms analogous to HD. Rats received either no implants or bilateral intrastriatal implants of polymers with or without QA. Subsequent tests for spontaneous motor activity (SMA), grip strength, balance, and learning ability in a radial-arm-water-maze task revealed QA-induced impairments in balance and learning ability, but did not affect grip strength or SMA. Histological analysis revealed QA-induced enlargement of lateral ventricles, striatal atrophy, and striatal neuronal loss, with relative sparing of NADPH-diaphorase-positive neurons. These results suggest that QA released from polymers can produce behavioral and neuropathological profiles analogous to early stages of HD and that EVA polymers offer a useful means of chronically delivering QA in rodent models of neurodegeneration.     

Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF transgenic mice: Trophic and tropic effects in a rodent model of Huntington's disease

The present study examined whether implants of epidermal growth factor (EGF)-responsive stems cells derived from transgenic mice in which the glial fibrillary acid protein (GFAP) promoter directs the expression of human nerve growth factor (hNGF) could prevent the degeneration of striatal neurons in a rodent model of Huntington's disease (HD). Rats received intrastriatal transplants of GFAP-hNGF stem cells or control stem cells followed 9 days later by an intrastriatal injection of quinolinic acid (QA). Nissl stains revealed large striatal lesions in rats receiving control grafts, which, on average, encompassed 12.78 mm³. The size of the lesion was significantly reduced (1.92 mm³) in rats receiving lesions and GFAP-hNGF transplants. Rats receiving QA lesions and GFAP-hNGF-secreting grafts stem cell grafts displayed a sparing of striatal neurons immunoreactive (ir) for glutamic acid decarboxylase, choline acetyltransferase, and neurons histochemically positive for nicotinamide adenosine diphosphate. Intrastriatal GFAP-hNGF-secreting implants also induced a robust sprouting of cholinergic fibers from subjacent basal forebrain neurons. The lesioned striatum in control-grafted animals displayed numerous p75 neurotrophin-ir (p75^NTR) astrocytes, which enveloped host vasculature. In rats receiving GFAP-hNGF-secreting stem cell grafts, the astroglial staining pattern was absent. By using a mouse-specific probe, stem cells were identified in all animals. These data indicate that cellular delivery of hNGF by genetic modification of stem cells can prevent the degeneration of vulnerable striatal neural populations, including those destined to die in a rodent model of HD, and supports the emerging concept that this technology may be a valuable therapeutic strategy for patients suffering from this disease. J. Comp. Neurol. 387:96–113, 1997. © 1997 Wiley-Liss, Inc.     

Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice

Huntington's disease (HD) is a progressive neurodegenerative disorder, characterized by severe degeneration of basal ganglia, motor abnormalities, impaired cognitive functions and emotional disturbances. Intrastriatal injection of the excitotoxin quinolinic acid (QA), an N-methyl-D-aspartate receptor agonist, appears to reproduce in rats some of the clinical features of human HD, included motor and behavioural deficits. Aim of this study was to assess whether the behavioural alterations described in the QA rat model of HD progressed over time. We analysed the effects of bilateral striatal injection of QA (300 nmol/1 microl) to adult rats in the spatial open-field test, a nonaversive task in which exploratory activity and responses to both spatial rearrangement of familiar objects and object novelty are measured. Rats were tested 2 weeks, 2 and 6 months after the QA lesion. Lesioned rats showed progressive alterations in performance in this task. Whereas sham and QA rats did not markedly differ 2 weeks post-lesion, lesioned rats were significantly more active than controls 2 and 6 months after surgery. Specifically, frequency and duration of rearing and wall rearing increased progressively over time, while grooming was enhanced at 2 months post-lesion only. Spatial and object novelty discrimination was not affected. These results show that a single injection of QA excitotoxin can induce behavioural changes that progress over time. The main implication of these findings is that, besides genetic mice models of HD, QA-lesioned rats may represent a suitable mean to test the ability of new drugs to slow down disease progression.     

Long-term cortical atrophy after excitotoxic striatal lesion: effects of intrastriatal fetal-striatum grafts and implications for Huntington disease

It is not currently clear whether the cortical atrophy observed in Huntington disease (HD) is entirely a direct consequence of the disease or at least partially a secondary consequence of striatal atrophy. This is of major importance for evaluating the possible therapeutic value of intrastriatal fetal-striatum grafts in HD. Cresyl violet-stained sections from rats that had received striatal excitotoxic lesions 1 wk or 4 wk previously showed small and statistically nonsignificant decreases in the thickness of cortical layers V and VI, while series from rats lesioned 12 months previously showed marked decreases in the thickness of the whole cortex (approximately 35% decrease), layer V (approximately 45%-50%) and layer VI (approximately 45%-50%), together with marked neuron loss in these layers. In deep layer V and layer VI, Fluoro-Jade staining showed labeled neurons in animals lesioned 1 wk previously, labeled neurons and astrocytes in animals lesioned 4 wk previously, and practically no labeling in animals lesioned 12 months previously. Intracortical injection of Phaseolus vulgaris leucoagglutinin revealed that corticostriatal fibers were practically absent from the lesioned area of striata lesioned 12 months previously. However, rats that received intrastriatal fetal-striatum grafts shortly after the lesion and were killed 12 months later showed a significant reduction in cortical atrophy, and a large number of labeled corticostriatal fibers surrounding and innervating the graft. In addition, a reduction in the number of Fluoro-Jade-labeled cells in the cortex was already apparent at 3 wk post-grafting. Regardless of whether HD has a primary effect on the cortex, the present results suggest that the striatal degeneration caused by HD contributes markedly to the cortical atrophy, and that intrastriatal grafts may ameliorate this secondary component of the cortical degeneration.     

Pain fibers contribute to the generation of subcortical somatosensory evoked potentials (SEPs) in rats

Subcortical somatosensory evoked potentials (SEPs) were obtained by electrical stimulation of the volar surface of the forepaw and were recorded from the skull overlying the contralateral somatosensory area of the cerebral cortex. Three distinct peaks were discernable in the SEPs prior to the first cortical component. Dorsal column transection at C3 level reduced the amplitude of component III by 48.7 +/- 4.7% without affecting the amplitude of components I and II. Morphine given either i.v. (2.5 mg/kg) or intrathalamically (25 microg/kg) almost completely abolished the part of component III that remained after surgical sectioning of the dorsal column of the spinal cord. The effects of morphine were reversed by i.v. naloxone (0.25 mg/kg). These results indicate that both the dorsal column and the anterolateral systems contribute significantly to the generation of component III of subcortical SEPs. Subcortical SEPs may be a useful non-invasive technique for studying the neurophysiological effects of known and experimental analgesics.     

Somatosensory evoked potential and clinical changes after electrode implant in basal ganglia of parkinsonian patients

Median nerve somatosensory evoked potentials (SEPs) were recorded in three parkinsonian patients who underwent electrode implant in the subthalamic nucleus and/or globus pallidus for chronic deep brain stimulation (DBS). SEPs were evoked before surgery, in a medication-free condition, and after the functional stereotactic procedure, before beginning DBS. In order to evaluate the timing of the SEP changes after the electrode implant, in three further patients SEPs were recorded within the operating theater, before and immediately after the implantation. Patients' symptoms improved immediately after the electrode implant, and both N20 and N30 amplitudes increased in the postsurgical SEP recording. The clinical and neurophysiological effects observed after surgery, before commencing DBS, can be explained by microdamage in the target nucleus following the electrode implant. They occurred also in the patients studied in the operating theater, thus suggesting that they occur immediately after the stereotactic procedure. Our results suggest that the circuitries between the basal ganglia and the primary sensorimotor cortex may be modified not only by DBS but also by microdamage due to surgery and that they exert an important influence on SEP amplitude.     

A role of the striatum in premotor cortical seizure development

Striatal function in partial seizure development induced by low frequency cortical stimulation of the ipsilateral premotor cortex was investigated by either electrolytic lesion placement or microinjection of putative neurotransmitter-related drugs into the ipsilateral striatum. Unilateral striatal lesioning and intrastriatal injection of muscimol, a GABA-agonist, and glutamic acid diethylester, a presumed antagonist for glutamatergic neurotransmission, were effective in suppressing seizure development, whereas intrastriatal injection of a subconvulsive dose of carbamylcholine chloride (carbachol), a cholinergic agonist, decreased the seizure threshold. In contrast to the ipsilaterally dominant metabolic activation in the intact animal, an inverse asymmetry due to a considerable reduction of deoxyglucose uptake in the ipsilateral thalamus, entopeduncular nucleus, substantia nigra, striatum and surrounding cortex of the focus was found in those brains with striatal lesion. Altogether, the findings suggest that experimental reduction of the inhibitory striatal outputs to both the entopeduncular nucleus and the substantia nigra enhances tonic activities of the projection GABAergic neurons in those nuclei, thereby inhibiting seizure development.     

Amelioration of behavioral deficits in a rat model of Huntington's disease by an excitotoxic lesion to the globus pallidus

Four groups of rats, sustaining a striatal quinolinic acid (QA) lesion, a pallidal QA lesion, a combined striatal + pallidal lesion, or sham operation, were tested in spontaneous and amphetamine-induced activity, spatial navigation in a water maze, position discrimination and reversal in a wet T maze, and food manipulation. The striatal lesion markedly impaired rats' performance on the motor and cognitive tasks. In contrast, rats sustaining a bilateral lesion to the GP in addition to the striatal lesion performed similarly to sham-operated rats on the motor and cognitive tasks, although they showed a transient decrease in activity levels. Given that a similar dysfunction of basal ganglia circuitry is thought to subserve the behavioral alterations seen in QA-lesioned rats and Huntington's disease (HD) patients, the present results raise the possibility that manipulations of the external segment of the globus pallidus (the primate analogue of the rat GP) could ameliorate some of HD symptoms.     

Prognostic value of early somatosensory evoked potentials in the presence of traumatic lesions of the spinal cord

Cortical and cervical early somatosensory evoked potentials (SEPs) were recorded after stimulation of median, ulnar, tibial or common peroneus nerves in 23 patients with traumatic paraplegia or quadriplegia. The clinical progress of these patients was followed for more than 18 months. The gradual clinical recovery or its absence was compared with neurophysiological data. In complete spinal injury, the absence of SEPs in response to stimulation of a nerve entering the cord below the level of injury demonstrates the high degree of spinal cord damage. There was a good correlation between the presence of SEP, even of low amplitude or long latency, and a favorable prognosis. The return of the SEP could herald clinical recovery of posterior column function. From a practical point of view, these preliminary data suggest that the investigation of early SEPs must begin with a very short delay after injury and be continued for approximately 6 months so that the irreversibility of the lesion can be clearly established.     

Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease

Huntington's disease (HD) is a progressive neurodegenerative disorder, characterised by severe degeneration of basal ganglia, motor abnormalities, impaired cognitive function and emotional disturbances. Many of the distinct neuropathological features of HD are reproduced in rats by intrastriatal injections of the excitotoxin quinolinic acid (QA), and QA-induced excitotoxicity is partially prevented by administration of the A(2A) receptor antagonist prior to the QA injection. In this study, we assessed the neuroprotective effects of the adenosine A(2A) receptor antagonist SCH 58261 on the progressive behavioural alterations reported in the QA rat model of Huntington's disease. Male rats received i.p. SCH 58261 (0.01mg/kg) or vehicle 20min before a bilateral injection of quinolinic acid (QA, 300nmol/1mul) or its vehicle in the dorsal striatum. Motor activity and anxiety levels were analyzed in an open-field arena and in an elevated plus-maze at 2 weeks, 2 months and 6 months post-lesion. In QA-lesioned rats SCH 58261 prevented alterations of wall rearing behaviour starting from 2 weeks post-lesion while emotional changes (reduced anxiety) were back to control levels by 6 months post-lesion. These findings extend to the behavioural parameters the protective effects of SCH 58261 in the QA model of Huntington's disease.     

Sleep stage dependant changes of the high-frequency part of the somatosensory evoked potentials at the thalamus and cortex.

OBJECTIVES: It is known that the high-frequency oscillations (above 400 Hz) of the somatosensory evoked potentials (SEPs) diminish during sleep while the N20 persists (Neurology 38 (1988) 64; Electroenceph clin Neurophysiol 70 (1988) 126; Electroenceph clin Neurophysiol 100 (1996) 189). We investigated possible differential effects of sleep on the 600 Hz SEPs at the thalamus and cortex. METHODS: SEPs from 10 subjects were recorded using 64 channels following electric stimulation at the wrist during awake state and sleep stages II, IV and REM. Dipole source analysis was applied to separate brain-stem, thalamic and cortical activity in the low-frequency (20-450 Hz) and the high-frequency (450-750 Hz) part of the signal. RESULTS: The low-frequency SEPs showed a non-significant increase of the latency of the N20 and a bifid change of the waveform in 3 subjects. The high-frequency SEPs showed a significant decrease of their amplitude at the level of the thalamus and cortex but not at the brain-stem. This decrease in amplitude at the thalamus and cortex were significantly correlated. There was no effect on the latency of the signal. In addition, at the cortex, differential effects on early and late parts of the 600 Hz oscillations were found by time-frequency analysis using a wavelet transformation. CONCLUSIONS: Sleep dependent decrease of the high-frequency SEPs were first observed at the thalamus pointing to the known function of the reticular thalamic nucleus regulating arousal. The results presented here provide further evidence for a thalamic origin of the 600 Hz oscillations. In addition, on the basis of the differential effects on early (up to the N20 peak) and late (between 20 and 25 ms) parts of the signal, at least one intracortical generator of these oscillations is proposed. In general, the high-frequency SEPs (600 Hz oscillations) are supposed to reflect activity of a somatosensory arousal system.     

Enkephalinergic striatal projection neurons become less affected by quinolinic acid than substance P-containing striatal projection neurons as rats age

While the excitotoxic vulnerability of striatal neurons is known to be greater in juvenile than adult animals, it is uncertain if striatal neuron types decline differentially in their vulnerability with age. To examine this issue, we unilaterally injected quinolinic acid (QA), an N-methyl-d-aspartate (NMDA) receptor agonist, into the striatum of juvenile and adult rats, and used in situ hybridization histochemistry with oligonucleotide probes for preproenkephalin and preprotachykinin mRNA to label surviving enkephalinergic (ENK) and substance P-containing (SP) neurons in adjacent sections through the injection center. The results confirmed that the region of severe damage is greater in young than adult animals, but revealed that at the very center of the QA injection, labeled neuron abundance was lower in adult than juvenile striatum. In juvenile rats, the vulnerability of the ENK neurons at all distances from the injection center was the same as that of the SP neurons. By contrast, in adult rats, the ENK neuron survival was greater than the SP neuron survival at all distances beyond the lesion center. The SP neuron survival outside the injection center in the adult rats was similar to that in juvenile rats, while the ENK neuron survival beyond the injection center was better in adult than juvenile rats. These data indicate that there is an age-dependent decrease in the vulnerability of ENK but not SP striatal projection neurons to QA-mediated injury in rats. The results also raise the possibility that, if an excitotoxic process is involved in HD pathogenesis, a differential age-related decline in the sensitivity of striatal projection neuron types to this process may contribute to the more uniform striatal neuron loss in juvenile-onset Huntington's disease (HD) and the more differential loss in adult-onset HD.     

The quinolinic acid model of Huntington's disease: locomotor abnormalities

In contrast to other excitotoxins, such as kainic acid, quinolinic acid (QA) may spare a specific population of striatal neurons that is also spared in Huntington's disease (HD). Although several histological and biochemical experiments support the use of QA as a model for HD, to date no behavioral experiments have been performed to examine the suitability of this model. The present study explored the behavioral effects of bilateral intrastriatal microinjections of four doses (75, 150, 225, 300 nmol) of QA in the male rat. Using a multidimensional analysis of spontaneous locomotion (Digiscan activity) and a record of metabolic indicators, such as weight loss, a dose-dependent effect was found. The 75-nmol dose had no significant effect on locomotion or feeding behavior. In contrast, the 150- and 225-nmol doses induced hyperactivity and weight loss, whereas the 300-nmol dose was lethal. The results obtained suggest that striatal injections of 150-225 nmol of QA induce behavioral deficits qualitatively similar though quantitatively less than those which are seen after similar injection of 3 nmol of kainic acid and which have been reported to be comparable to the symptomatology of HD. Together with QA's possible greater histological selectivity, the present results support the use of QA-induced striatal lesions as a behavioral model of Huntington's disease.     

Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion

We examined the expression of TNF-alpha within the substantia nigra pars reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and studied the effect of rolipram, a TNF-alpha-inhibitor, on the secondary neuronal damage. QA (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. After survival of 1, 3 or 10 days, the animals were sacrificed and immunohistochemical staining with an antibody against TNF-alpha was performed. From day 1 to day 10 after striatal QA injection TNF-alpha positive cells were observed within ipsilateral substantia nigra which were neither present on the contralateral side nor in sham-operated controls. Double labeling with antibodies against TNF-alpha and NeuN, keratan sulfate proteoglycan or GFAP displayed a good overlap between TNF-alpha and NeuN, which suggests that TNF-alpha positive cells are neurons. For the pharmacological approach, three groups of QA rats were treated intraperitoneally with either solvent (n=5), the NMDA receptor antagonist MK 801 (4 mg/kg, n=6) or the TNF-alpha inhibitor rolipram (0.3 mg/kg, n=6), which was started 24 h after QA-injection and continued with daily applications for 14 days. The amount of striatal damage did not differ between the three groups. The number of intact neurons within the ipsilateral substantia nigra of the solvent treated group was reduced by approximately 30% compared to the contralateral side. Both MK 801 and rolipram ameliorated this secondary damage and reduced the number of TNF-alpha positive cells. The observed association between expression of TNF-alpha and secondary neuronal damage within the substantia nigra induced by intrastriatal QA application might hint towards an involvement of this cytokine in transneuronal degeneration.     

Abnormalities of parietal and prerolandic somatosensory evoked potentials in Huntington's disease.

Cervical, parietal and prerolandic somatosensory evoked potentials (SEPs) to median nerve stimulation at the wrist were recorded with an earlobe reference in 24 patients with Huntington's disease (HD) and in 24 age-matched normal controls. Cortical responses of abnormal wave form and reduced amplitude were constantly observed in HD patients. SEP changes affected more severely the prerolandic (P22/N30) pattern, which could not be recognized in two-thirds of patients, than the parietal (N20/P27) pattern, which could be identified in all cases. The N20 latency and the central conduction time (N13-N20 interval) were significantly increased. The occurrence of abnormalities of central conduction and of a predominant involvement of the prerolandic SEP pattern suggests an impairment of impulse transmission along the somatosensory lemniscal pathway at subcortical, possibly thalamic, level in HD.     

Neuronal organization of rat thalamus for processing information of vibrissal movements

Vibrissa-responding neurons were searched for in the somatosensory part of the thalamic reticular nucleus (S-TR) and in the ventrobasal nucleus (VB) in urethane-anesthetized rats. More than 90% of the recorded neurons of both species had receptive fields (RFs) on single vibrissae. Movements of RF-vibrissae produced a burst of multiple discharges in S-TR neurons and single spike discharges followed by a prominent suppression of spontaneous discharges in VB neurons. Antidromic invasion from stimulation of the somatosensory cortex in VB neurons was suppressed after RF-vibrissae were stimulated. A possible functional organization comprising VB and S-TR neurons for processing impulses of vibrissal movements was suggested.