The role of the substantia nigra in a striatally-evoked motor response in the rat: effects of intranigral drugs and lesions

Turning of the head towards the contralateral side was induced in the conscious unrestrained rat by electrical stimulation of the neostriatum through permanent indwelling electrodes. The importance of the substantia nigra in mediating this response was investigated using electrolytic and kainic acid lesions. Contralateral head-turning was attenuated by small electrolytic lesions of the substantia nigra on the stimulated side and abolished by large electrolytic lesions that destroyed the entire nucleus. The injection of kainic acid into the substantia nigra caused persistent circling behaviour but did not modify the head-turn response to striatal stimulation; these injections destroyed some of the neurons in the pars compacta but the majority of neurons in the pars reticulata were undamaged. Drugs that alter the function of nigral neurotransmitters were injected through an indwelling cannula in the zona reticulata. Interference with the function of γ-aminobutyrate in the nigra produced small changes in the latency of the motor response. However the following drugs did not modify the response: substance P, nicotine, atropine, apomorphine, glutamic acid diethylester, glycine, strychnine, met-enkephalin and 5-methoxy-N,N-dimethyltryptamine.It is concluded that descending projections from the basal ganglia which pass through or very close to the nigra, probably without forming synapses in the pars reticulata, may be important for the mediation of the striatally-evoked response.     

Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat

Electrophysiological recordings were made in anaesthetized rats to investigate the mode of function of high-frequency stimulation of the subthalamic nucleus used as a therapeutic approach for Parkinson's disease. High-frequency electrical stimulation of the subthalamic nucleus (130 Hz) induced a net decrease in activity of all cells recorded around the site of stimulation in the subthalamic nucleus. It also caused an inhibition of the majority of neurons recorded in the substantia nigra pars reticulata in normal rats (94%) and in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (90%) or with ibotenic acid lesions of the globus pallidus (79.5%). The majority of cells recorded in the ventrolateral nucleus of the thalamus responded with an increase in their activity (84%).These results show that high-frequency stimulation of the subthalamic nucleus induces a reduction of the excitatory glutamatergic output from the subthalamic nucleus which results in deactivation of substantia nigra pars reticulata neurons. The reduction in tonic inhibitory drive of nigral neurons induces a disinhibition of activity in the ventrolateral motor thalamic nucleus, which should result in activation of the motor cortical system.     

Regional differences in the cat caudate nucleus as to the effectiveness in inducing contraversive head-turning by electrical stimulation

An attempt was made to re-examine regional differences in the cat caudate nucleus as to the effectiveness in inducing contraversive head-turning by electrical stimulation and to analyze the time course of head-turning quantitatively. In 5 of the total 9 cats, the right sensorimotor cortex and its surrounding areas had been ablated chronically. While the awake, unrestrained cat maintained a stable standing posture facing forward, stimulation was applied systematically to various points in and around the caudate nucleus with a movable stimulating electrode. Trains of stimulating current pulses of less than 300 microA were given, mostly at a rate of 100 Hz for 5 s. In most experiments in which stimulation was given to the side of the intact cerebral cortex, stimulation of caudal portions of the head of the caudate nucleus was effective in inducing contraversive head-turning, but that of its rostral portions was ineffective. In experiments on the side of chronic cortical ablation, similar results were obtained. These results suggested that head-turning induced by stimulation of the caudate nucleus was brought about not by the activation of the corticofugal fibers from these cortical areas by a current spreading to the internal capsule, but by the activation of caudate neurons. Hence, it was demonstrated that there were regional differences in the cat caudate nucleus as to the effectiveness in inducing head-turning. The mean of the shortest latencies of the onset of head-turning for individual stimulation points was 396 ms (S.D., 210 ms) for the side of the intact cerebral cortex, and 454 ms (S.D., 289 ms) for the side of the cortical ablation. Statistically, there was no significant difference between them. Therefore, it was further revealed that the elimination of the sensorimotor cortex did not affect the caudate-induced head-turning in terms of the latency of its onset.     

Movement disorders and lesions of pigeon brain stem analogues of basal ganglia

The nucleus spiriformis lateralis (SpL) and the nucleus tegmenti pedunculo-pontinus, pars compacta (TPc) of the pigeon are thought to be analogous to the mammalian substantia nigra. The analogy is based upon comparative neuroanatomical and histochemical similarities. To test the analogy on a behavioral basis, unilateral electrolytic or kainate lesions were produced in selected nuclei of the diencephalon and mesencephalon. Birds demonstrated behaviioral disturbances similar to those induced in mammals after lesions to the substantia nigra. The most obvious disturbance was a persistent turning in a direction opposite to the side of the lesion. The birds also demonstrated postural problems and arhythmic movements of the head or whole body tremor. The similarities in movement disorders strengthen on a behavioral basis, the suggested analogies between the mammalian substantia nigra and the SpL and TPc. The pigeon may be another useful experimental model to study movement disorders associated with damage to the basal ganglia.     

Selective bilateral destruction of substantia nigra has no effect on kindled seizures induced from stimulation of amygdala or piriform cortex in rats

Enhancement of GABAergic transmission in the substantia nigra has been shown to attenuate motor manifestations of diverse seizure models, including kindling. Similar anticonvulsant effects were reported after bilateral lesions of the substantia nigra, supporting the view that the nigra efferents constitute a critical gating mechanism in the propagation of seizure activity. However, in the lesion studies reported so far the nigra was not destroyed selectively so that regions destroyed in addition to the nigra could have been involved in the anticonvulsant effects observed. We destroyed the nigra selectively in fully kindled rats by bilateral microinjection of small amounts of the neurotoxin ibotenic acid. Two groups of rats were studied; one was kindled from stimulation of the basolateral amygdala, the other from stimulation of the piriform cortex. In both groups, there was no indication of a reduction in seizure susceptibility, seizure severity or seizure duration after bilateral destruction of the nigra. The data thus indicate that, at least in kindled rats, the substantia nigra might be less important for seizure generation and/or propagation than previously thought.     

The anatomical substrate of the turning behaviour seen after lesions in the nigrostriatal dopamine system

Studies of the fibre connections of the substantia nigra suggest that the behavioural results of changes in the activity in the striatal dopamine-containing system are mediated by a pathway from the striatum to the substantia nigra and thence to the thalamus. Small discrete electrolytic lesions in the appropriate part of the crus cerebri interrupt the striatonigral axons without damage to the nigrostriatal system. Such lesions inhibit turning induced by activation of striatal dopamine receptors.Similarly, turning induced by apomorphine in rats lesioned with 6-hydroxydopamine is inhibited by damage to the ipsilateral ventromedial area of thalamus which receives fibres from the substantia nigra.     

Striatal grafts in rats with unilateral neostriatal lesions--II. In vivo monitoring of GABA release in globus pallidus and substantia nigra

GABA release was recorded in vivo by push-pull perfusion from the globus pallidus and substantia nigra of control rats, rats with unilateral ibotenic acid lesions of the neostriatum, and rats with embryonic striatal tissue grafts implanted in the lesioned striatum. The lesions reduced baseline levels of GABA release to 5% of control levels in the globus pallidus and to 13% of control levels in the substantia nigra pars reticulata. GABA release was substantially restored in both the globus pallidus and substantia nigra of the grafted rats, to 34 and 60%, respectively. Peripheral injection of the dopaminergic stimulant methamphetamine induced a short (lasting approximately 20 min) 4-5 fold increase in GABA release in the intact globus pallidus and a longer (lasting longer than 80 min) increase in the substantia nigra. The stimulatory effect of methamphetamine on GABA release was completely abolished in both sites by the strial lesions, suggesting that the effect was mediated via a direct or indirect dopaminergic action on striatal output neurons. The grafts reinstated methamphetamine-induced stimulation of GABA release in striatal output targets to a level (as a proportion of baseline) that was similar to that seen in the control rats. The results support the view that activation of the dopaminergic inputs to the striatum is functionally excitatory on the major striatal output projections to the globus pallidus and substantia nigra pars reticulata. The results also support the hypothesis that striatal grafts have the capacity to become functionally incorporated by reciprocal graft-host connections into the neural circuitry of the host brain.     

Topographic and functional neuroanatomical study of GABAergic disinhibitory striatum-nigral inputs and inhibitory nigrocollicular pathways: neural hodology recruiting the substantia nigra, pars reticulata, for the modulation of the neural activity in the inferior colliculus involved with panic-like emotions

Considering the influence of the substantia nigra on mesencephalic neurons involved with fear-induced reactions organized in rostral aspects of the dorsal midbrain, the present work investigated the topographical and functional neuroanatomy of similar influence on caudal division of the corpora quadrigemina, addressing: (a) the neural hodology connecting the neostriatum, the substantia nigra, periaqueductal gray matter and inferior colliculus (IC) neural networks; (b) the influence of the inhibitory neostriatonigral-nigrocollicular GABAergic links on the control of the defensive behavior organized in the IC. The effects of the increase or decrease of activity of nigrocollicular inputs on defensive responses elicited by either electrical or chemical stimulation of the IC were also determined. Electrolytic or chemical lesions of the substantia nigra, pars reticulata (SNpr), decreased the freezing and escape behaviors thresholds elicited by electrical stimulation of the IC, and increased the behavioral responses evoked by the GABAA blockade in the same sites of the mesencephalic tectum (MT) electrically stimulated. These findings were corroborated by similar effects caused by microinjections of the GABAA-receptor agonist muscimol in the SNpr, followed by electrical and chemical stimulations of the IC. The GABAA blockade in the SNpr caused a significant increase in the defensive behavior thresholds elicited by electrical stimulation of the IC and a decrease in the mean incidence of panic-like responses induced by microinjections of bicuculline in the mesencephalic tectum (inferior colliculus). These findings suggest that the substantia nigra receives GABAergic inputs that modulate local and also inhibitory GABAergic outputs toward the IC. In fact, neurotracing experiments with fast blue and iontophoretic microinjections of biotinylated dextran amine either into the inferior colliculus or in the reticular division of the substantia nigra demonstrated a neural link between these structures, as well as between the neostriatum and SNpr.     

Behavioral and electrophysiological changes following microinjections of colchicine into the substantia nigra.

Male Sprague-Dawley rats received bilateral microinjections of colchicine (2 or 4 μg in 1 μl) into the substantia nigra. During the first 2 days the animals were hyperactive, intense gnawing and chewing were observed, and food intake was significantly increased. During the next 3 or 4 days, activity, food and water intakes and body weight gain were markedly reduced; the behavior was similar to that previously observed following damage to the substantia nigra and nigrostriatal pathway from 6-hydroxydopamine or electrolytic lesions. This period of hypophagia and hypodipsia was followed by a rebound increase in food and water intake for several days until body weight returned to normal levels. Field potentials recorded from the caudate nucleus in response to electrical stimulation of the substantia nigra were reduced in amplitude during the first 4 days following microinjections of colchicine into the substantia nigra and recovered by Day 7.These reversible behavioral effects of microinjections of colchicine into the substantia nigra confirm the importance of the nigrostriatal pathway in motor and ingestive behaviors.     

Substantia nigra stimulation evoked antidromic responses in rat neostriatum

Summary Electrical stimulation of the substantia nigra of rats elicits a burst of small amplitude waves with a latency of 4–6 ms that may last for 10–15 ms throughout much of the neostriatum. Frontal cortex stimulation also elicits a burst response, which can occlude the substantia nigra response. The substantia nigra evoked burst response was still present after chronic neocortical ablation or thalamic transection or both treatments combined. The response corresponds to the first sharp negative wave of the substantia nigra evoked neostriatal field potential. Single substantia nigra evoked action potentials were recorded in neostriatum with a mean latency of 9.8 ms, ranging from 4–22 ms. These action potentials were considered to be antidromic because 1) they were occluded during appropriate collision intervals by orthodromic action potentials elicited by frontal cortex stimulation. Subthreshold frontal cortex conditioning stimulation did not alter the threshold for activation from substantia nigra. The refractory period for the axon was at least as long as that for the soma and ranged between 0.8–2.0 ms. The antidromic responses failed to follow low frequency stimulation (< 40 Hz for 3000 ms). This failure occurred in the axon between substantia nigra and globus pallidus. The burst response and first sharp negative wave of the field potential probably represent the antidromic activation of the ubiquitous and densely packed medium spiny neostriatal projection neurons. These responses 1) occur at the same latency, 2) respond in the same manner to twin pulse and repetitive stimulation and 3) are occluded by frontal cortex stimulation in the same manner as antidromic action potentials.     

Rotometer for recording rotation in chemically or electrically stimulated rats

An improved rotometer is described which accurately records circling behavior (rotation) in rats with an imbalance of the nigrostriatal pathways. Results of circling induced by apomorphine in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra and circling elicited by electrical stimulation of the nigrostriatal pathway are presented.     

Nigral dopamine autoreceptors are exclusively of the D2 type: quantitative autoradiography of [125I]iodosulpride and [125I]SCH 23982 in adjacent brain sections

The effect of unilateral 6-hydroxydopamine lesions of the medial forebrain bundle on the specific binding of [125I]iodosulpride and [125I]SCH 23982 in the rat substantia nigra was determined by quantitative autoradiography of adjacent sections. The specific binding of [125I]iodosulpride was reduced by 40-70% on the lesioned side in the substantia nigra pars compacta, reticulata, lateralis and in the ventral tegmental area. In contrast, the specific [125I]SCH 23982 binding was unchanged in all subdivisions of the substantia nigra. The results indicate that dopamine autoreceptors are present in the substantia nigra and in the ventral tegmental area and that they are exclusively of the D2 type.     

L-dopa stimulates the release of [3H]gamma-aminobutyric acid in the basal ganglia of 6-hydroxydopamine lesioned rats

L-DOPA stimulated the K(+)-induced [3H]GABA (gamma-aminobutyric acid) release from slices of substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen isolated from the ipsilateral side of 6-hydroxydopamine-lesioned rats, but the release from ipsilateral subthalamic slices was not affected. In substantia nigra, L-DOPA stimulation (EC50 = 1 microM) of [3H]GABA release was dose-dependently blocked (IC50 = 0.1 microM for the stimulation caused by 10 microM L-DOPA) by the D1 antagonist SCH 23390, but was not affected by (-)-sulpiride, a D2 antagonist. SCH 23390 also blocked the stimulation in the other nuclei. The DOPA decarboxylase inhibitor NSD-1015 (500 microM) did not prevent the stimulation induced by L-DOPA in all of the studied nuclei. The results suggest that L-DOPA is able to activate D1 receptors located on the terminals of striatal projections via the dopamine formed by a decarboxylation mediated by an NSD-1015-resistant enzyme. Activation of the presynaptic D1 receptors results in stimulation of GABA release.     

Striatal, pallidal, and pars reticulata evoked inhibition of nigrostriatal dopaminergic neurons is mediated by GABA(A) receptors in vivo

Dopaminergic neurons express both GABA(A) and GABA(B) receptors and GABAergic inputs play a significant role in the afferent modulation of these neurons. Electrical stimulation of GABAergic pathways originating in neostriatum, globus pallidus or substantia nigra pars reticulata produces inhibition of dopaminergic neurons in vivo. Despite a number of prior studies, the identity of the GABAergic receptor subtype(s) mediating the inhibition evoked by electrical stimulation of neostriatum, globus pallidus, or the axon collaterals of the projection neurons from substantia nigra pars reticulata in vivo remain uncertain. Single-unit extracellular recordings were obtained from substantia nigra dopaminergic neurons in urethane anesthetized rats. The effects of local pressure application of the selective GABA(A) antagonists, bicuculline and picrotoxin, and the GABA(B) antagonists, saclofen and CGP-55845A, on the inhibition of dopaminergic neurons elicited by single-pulse electrical stimulation of striatum, globus pallidus, and the thalamic axon terminals of the substantia nigra pars reticulata projection neurons were recorded in vivo. Striatal, pallidal, and thalamic induced inhibition of dopaminergic neurons was always attenuated or completely abolished by local application of the GABA(A) antagonists. In contrast, the GABA(B) antagonists, saclofen or CGP-55845A, did not block or attenuate the stimulus-induced inhibition and at times even increased the magnitude and/or duration of the evoked inhibition. Train stimulation of globus pallidus and striatum also produced an inhibition of firing in dopaminergic neurons of longer duration. However this inhibition was largely insensitive to either GABA(A) or GABA(B) antagonists although the GABA(A) antagonists consistently blocked the early portion of the inhibitory period indicating the presence of a GABA(A) component. These data demonstrate that dopaminergic neurons of the substantia nigra pars compacta are inhibited by electrical stimulation of striatum, globus pallidus, and the projection neurons of substantia nigra pars reticulata in vivo. This inhibition appears to be mediated via the GABA(A) receptor subtype, and all three GABAergic afferents studied appear to possess inhibitory presynaptic GABA(B) autoreceptors that are active under physiological conditions in vivo.     

Evidence that [3H]forskolin binding in the substantia nigra is intrinsic to a striatal-nigral projection: an autoradiographic study of rat brain

The neuronal localization of binding sites for the diterpene activator of adenylate cyclase, forskolin, has been determined. Kainic or ibotenic acid lesions were administered into the caudate-putamen or substantia nigra of Sprague-Dawley rats. The binding of 20 nM [3H]forskolin was examined autoradiographically and quantitated using computerized densitometry with tritium standards. Neurochemical lesions placed in the caudate-putamen markedly reduced [3H]forskolin binding in this structure and distal to the site of injection in the substantia nigra. Ibotenic acid lesions placed in the substantia nigra did not appreciably alter binding in the substantia nigra, caudate-putamen, nucleus accumbens or olfactory tubercle. These results indicate that 'forskolin-identified' adenylate cyclase in the substantia nigra is located in nerve terminals from the caudate-putamen. In addition, these sites are presumably located on cell bodies or interneurons in the caudate-putamen.     

Abortive amygdaloid kindled seizures following micro-injection of γ-vinyl-GABA in the vicinity of substantia nigra in rats

The effects of microinjection of a GABA-elevating substance (γ-vinyl-GABA) in the substantia nigra were assessed on kindled convulsive seizures induced by daily appropriate amygdaloid stimulation in the rat. Bilateral administration of 20 μg of γ-vinyl-GABA strongly reduced the afterdischarge duration of the seizures without significantly modifying the motor convulsions. This effect was noted 24 h after injection and lasted for up to 48 h. Administration of γ-vinyl-GABA in structures 1.5 mm distant from the substantia nigra had no effect on kindled seizures. It is suggested that the substantia nigra may intervene in a negative feedback system that tends to suppress the paroxysmal activity initiated from the amygdala.     

Striato-nigral dynorphin and substance P pathways in the rat

The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Caudate stimulation and substantia nigra activity in the rat.

1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed.     

Inhibition of the substantia nigra suppresses absences and clonic seizures in audiogenic rats, but not tonic seizures: evidence for seizure specificity of the nigral control

GABAergic inhibition of the substantia nigra pars reticulata has been shown to suppress seizures in most models of epilepsy involving forebrain networks, such as absences or clonic seizures. No such antiepileptic effects were observed, however, in genetically audiogenic rats exhibiting tonic seizures generated in the brainstem. This suggests a constitutive dysfunction of the nigral GABAergic neurotransmission in this strain of rat or a selective action of the nigral control on specific networks. In the present study, we first confirmed that bilateral injection of muscimol (700 pmol/side) in the substantia nigra had no effect in Wistar rats with audiogenic seizures (Wistar AS). [3H]Muscimol autoradiography suggested a 40% reduced density of GABA(A) receptors in the substantia nigra of Wistar AS, whereas no change was observed in the cortex and the superior colliculus (superficial and intermediate layers), as compared to control animals. In Wistar AS where 40 repetitions of audiogenic stimulations progressively induced generalised convulsive seizures with both tonic and clonic components, bilateral injection of muscimol (350 pmol/side) in the substantia nigra suppressed the clonic component but had no effect on tonic seizures. In hybrid rats issued from cross-breeding between Wistar AS and rats with spontaneous absence seizures, bilateral injection of muscimol (18 pmol/side) in the substantia nigra abolished cortical spike-and-wave discharges, but had no effect on tonic audiogenic seizures at doses up to 700 pmol/side. These results show that despite a decreased number of GABA(A) receptors in the substantia nigra, inhibition of this structure in Wistar AS still leads to inhibition of seizures involving forebrain structures. These results confirm that GABAergic inhibition of the substantia nigra has antiepileptic effects through the control of forebrain circuits. They suggest that this control mechanism has no inhibitory effect on circuits underlying audiogenic tonic seizures.     

Cortical stimulation induces fos expression in striatal neurons.

Electrical stimulation of a broad area of the frontoparietal cortex in the rat brain induces immunocytochemically detectable Fos in striatal neurons normally devoid of the protein. The vividness of labeling within striatal neurons was maximal at 0.5 h after the cessation of a 15-min-long stimulation period and became weaker by 3 h. Although Fos-reactive neurons were widely distributed in the striata of both hemispheres in an uneven pattern, those on the stimulated side were more numerous and more darkly stained. At no time-point were labeled neurons found in the globus pallidus, entopeduncular nucleus or substantia nigra. Destruction of the nigrostriatal dopamine projection with 6-hydroxydopamine did not induce Fos production and failed to prevent the induction of Fos by cortical stimulation. That many of the Fos-positive neurons project to the substantia nigra was confirmed by retrograde labeling with Fluoro-Gold. The data suggest that corticostriatal excitatory transmission may directly influence the genomic activity of striatal neurons by way of Fos.