Separate neuronal populations of the rat substantia nigra pars lateralis with distinct projection sites and transmitter phenotypes.

The topographic organization of the nigral cells sending axons to the striatum, amygdala and inferior colliculus was studied in the rat substantia nigra pars lateralis by using retrograde fluorescent tracers. Nigral perikarya projecting to the inferior colliculus were located dorsolaterally within the substantia nigra pars lateralis, whereas nigral perikarya projecting to the striatum or to the amygdala were mostly situated ventromedially within the substantia nigra pars lateralis. The transmitter substances of the nigrotectal cells were examined by combining a retrograde tracing method with immunohistochemistry for tyrosine hydroxylase or glutamate decarboxylase. Nigral neurons projecting to the inferior colliculus lacked tyrosine hydroxylase immunoreactivity, but exhibited immunoreactivity for glutamate decarboxylase. The substantia nigra pars lateralis is made up of different neuronal populations: one projecting to the inferior colliculus and another directed to the striatum and amygdala. The pars lateralis pathway to the inferior colliculus utilized GABA as a neurotransmitter, whereas the previously characterized nigral cells projecting to the striatum and superior colliculus use GABA and dopamine as neurotransmitters.     

Topographic projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta of the cat with special reference to pallidal projections

Summary Projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta (TPC) were studied by using anterograde and retrograde tracing techniques with horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the cat. Following WGA-HRP injections into the medial TPC area, a substantial number of retrogradely labeled cells were seen in the entopeduncular nucleus (EP) and medial half of the substantia nigra pars reticulata (SNr), whereas following WGA-HRP injections into the lateral TPC area, labeled cells were marked in the caudal half of the globus pallidus (GP) and lateral half of the SNr. To confirm the retrograde tracing study, WGA-HRP was injected into the EP or the caudal GP, and anterograde labeling was observed in the TPC areas. Terminal labeling was located in the medail TPC area in the EP injection case, while terminal labeling was observed in the lateral TPC area in the caudal GP injection case. Projections from the striatum to the pallidal complex (the EP and the caudal GP) were also studied autoradiographically by injecting amino acids into various parts of the caudate nucleus and the putamen. Terminal labeling was distributed over the whole extent of the EP and the rostral GP following injections into the rostral striatum (the head of the caudate nucleus or the rostral part of the putamen), while terminal labeling was distributed over the caudal GP following injections into the caudal striatum (the body of the caudate nucleus or the caudal part of the putamen). From these findings, we conclude that there exists a medio-lateral topography in the projection from the basal ganglia to the TPC: The EP receives afferent projections from the rostral striatum and projects to the medial TPC area, whereas the caudal GP receives projections from the caudal striatum and sends fibers to the lateral TPC area.Abbreviations BC brachium conjunctivum - CD caudate nucleus - CP cerebral peduncle - DBC decussation of the brachium conjunctivum - EP entopeduncular nucleus - GP globus pallidus - IC internal capsule - ICo inferior colliculus - LH lateral habenular nucleus - ML medial lemniscus - PN pontine nuclei - PUT putamen - SCo superior colliculus - SI substantia innominata - SN substantia nigra - SNc substantia nigra pars compacta - SNr substantia nigra pars reticulata - STN subthalamic nucleus - TH thalamus - TPC nucleus tegmenti pedunculopontinus pars compacta     

Subthalamic nucleus efferent projection to the cerebral cortex

A direct projection from the subthalamic nucleus to the dorsal cerebral cortex has been demonstrated in the rat using a retrograde axonal transport technique. Injections of horseradish peroxidase into the cerebral cortex gave rise to retrogradely-labelled neuronal cell bodies in the ipsilateral subthalamic nucleus. Labelled cells were restricted to the lateral half of the nucleus. In addition, retrograde-labelling was observed in the rostral and caudal portions of the entopeduncular nucleus. Injections of horseradish peroxidase into the striatum underlying the cortical region receiving subthalamic efferents failed to label any subthalamic nucleus or entopeduncular nucleus neurones.These findings add the cerebral cortex to the other known projection areas (globus pallidus, substantia nigra, nucleus tegmenti pedunculopontinus) of the subthalamic nucleus and might have implications for the way in which the subthalamic nucleus influences motor activity.     

An electrophysiological study of thalamo-caudate neurones in the cat

Summary Thalamo-caudate projection neurones were identified in cats by antidromic activation from the caudate nucleus, under chloralose anaesthesia or in cerveau isolé preparations.Units in nuclei centralis lateralis, medialis dorsalis, and centrum medianum-parafascicularis responded antidromically to one or more electrodes of a caudate nucleus array at latencies ranging from 0.4 to 16 ms. The responses did not appear to result from stimulus spread to the internal capsule.A separate population of medial thalamic units responded post-synaptically to caudate stimulation, at modal latency exceeding modal antidromic latency by 2 ms. Comparison of apparent conduction velocities for each thalamic nucleus indicated that the postsynaptic responses were activated by collaterals of thalamo-caudate neurones.A proportion of thalamo-caudate neurones responded to somatic stimulation; some of these were inhibited by caudate stimulation, and a few discharged on substantia nigra stimulation. These results demonstrate the possibility of somatic afferent and nigrofugal inputs to the caudate nucleus mediated by neurones of the medial thalamus.     

Basal ganglia and other afferent projections to the peribrachial region in the rat: A study using retrograde and anterograde transport of horseradish peroxidase

The afferent projections to the peribrachial region in the rat were studied using retrograde and anterograde transport of horseradish peroxidase. Particular attention was paid to descending projections from the basal ganglia and related nuclei to the region of nucleus tegmenti pedunculopontinus. Following injection of peroxidase into nucleus tegmenti pedunculopontinus, few retrogradely-labelled neurons were found in the entopeduncular nucleus proper, but larger numbers were found with a wide distribution within the boundaries of the internal capsule and cerebral peduncle. Labelled cells were also consistently observed in the amygdala, the caudal globus pallidus, the subthalamus including zona incerta and subthalamic nucleus, the hypothalamus, the substantia nigra and the ventral tegmental area. Following iontophoretic injections of horseradish peroxidase into the entopeduncular nucleus, lateral hypothalamus, subthalamic nucleus or ventral tegmental area, terminal labelling was observed in and around the branchium conjunctivum in an area apparently corresponding to nucleus tegmenti pedunculopontinus in the rat.     

Efferent fiber projections of the habenula and the interpeduncular nucleus. An experimental study in the opossum and cat

Summary A study of efferent fiber connections of the habenula and the inter-peduncular nucleus was conducted using anterograde degeneration techniques. Lesions were placed in the habenula of the opossum and the habenula and interpeduncular nucleus of the cat. Degeneration was studied by means of the Nauta and Fink-Heimer techniques.Fibers from the habenular nucleus of the opossum extended caudally and were traced bilaterally to the interpeduncular nucleus, dorsal tegmental nucleus of Gudden, deep (ventral) tegmental nucleus of Gudden, nucleus centralis superior and nucleus reticularis tegmenti pontis. Rostrally fibers were traced to the preoptic and septal region and the anterior and lateral hypothalamus.The medial and lateral habenular nuclei of the cat projected differentially to portions of the interpeduncular nucleus and the tegmental nuclei of Gudden. The medial habenular nucleus sent fibers to the paramedian subnucleus of the interpeduncular nucleus and to the deep tegmental nucleus; whereas the lateral habenular nucleus distributed to the apical and central subnuclei of the interpeduncular nucleus and the dorsal tegmental nucleus.Fibers from both the medial and lateral habenular nuclei were found to project bilaterally to the nucleus paraventricularis anterior, nucleus ventralis anterior, anterior medialis and anterior dorsalis of the thalamus, and the septal area.Fibers from the interpeduncular nucleus of the cat were represented bilaterally. Those passing rostral went to the lateral habenular nucleus, nucleus centromedianus and parafascicularis of the thalamus, and to the septal area. Those directed caudally projected to the nucleus centralis superior, and the dorsal and deep tegmental nucleus of Gudden.Abbreviations AC anterior commissure - AD nucleus anterior dorsalis - AM nucleus anterior medialis - AV nucleus anterior ventralis - BC brachium conjunctivum - CC corpus callosum - CD caudate nucleus - CI internal capsule - CL nucleus centralis lateralis - CM nucleus centromedianus - CP cerebral peduncle - DT dorsal tegmental nucleus (of Gudden) - EN entopeduncular nucleus - Fx fornix - GC central gray - GL lateral geniculate nucleus - GM medial geniculate nucleus - GP globus pallidus - HbPt habenulopeduncular tract - HVM ventromedial hypothalamic nucleus - IC inferior colliculus - IP interpeduncular nucleus - LHb lateral habenular nucleus - LL lateral lemniscus - LMN lateral mammillary nucleus - LP nucleus lateralis posterior - MD nucleus medialis dorsalis - MHb medial habenular nucleus - ML medial lemniscus - MMN medial mammillary nucleus - MP mammillary peduncle - NCM nucleus centralis medialis - OC optic chiasm - OT optic tract - Pf nucleus parafascicularis - Pul pulvinar - PUT putamen - RE nucleus reuniens - RN red nucleus - RPO preoptic area - RTP nucleus reticularis tegmenti pontisv (von Bechterew) - S stria medullaris - SC superior colliculus - SN substantia nigra - SPT septal area - VA nucleus ventralis anterior - VL nucleus ventralis lateralis - VM nucleus ventralis medialis - VPL nucleus ventralis posterolateralis - VPM nucleus ventralis posteromedialis - VT deep tegmental nucleus (of Gudden) - II optic nerve     

Spatio-temporal organization of a branched tecto-spinal/ tecto-diencephalic neuronal system

The aim of the present study was to identify in the rat the diencephalic nuclei addressed by ascending collaterals of tecto-spinal neurons. For this purpose we made use of the anterograde axonal transport method to determine the pattern of diencephalic projections arising from the lateral portion of the superior colliculus where most of tecto-spinal neurons are lying. Next, we used the antidromic activation method to analyse whether some of these colliculo-diencephalic projections were provided through collaterals of tecto-spinal neurons.Following injections of wheatgerm agglutinin, conjugated with horseradish peroxidase, in the lateral part of the superior colliculus, anterograde labelling was observed in: the contralateral superior colliculus, the ipsilateral pretectal nuclei, subthalamic area (zona incerta and Forel field) and thalamic structures namely: dorsal and ventral lateral geniculate, parafascicular, posterior nuclear group, reuniens nuclei and lateral portion of medio-dorsal nucleus. Moreover, bilateral projections were revealed in the following thalamic nuclei: lateral posterior, ventro-medial, paracentral and central-lateral.In the electrophysiological study we established that the thalamic nuclei medio-dorsal/central-lateral, paracentral, ventral-medial and the zona incerta receive ascending collaterals of the tecto-spinal neurons. In addition, an axonal branch to the contralateral superior colliculus was also revealed. The various ascending and descending collaterals of each branched neuron exhibited a similar conduction time for action potentials. It is thus likely that the tecto-spinal/tecto-diencephalic neurons provide a synchronized influence on their targets.The functional implication of such a branched collicular efferent pathway is discussed. Considering that tecto-spinal neurons are one of the collicular neuronal populations on which the substantia nigra exerts its influence, new perspectives in the analysis of basal ganglia collicular relationships are given.     

Regulation of cerebello-cortical transmission in the rat ventromedial thalamic nucleus

Summary On the basis of antidromic stimulation we have identified two distinct neuronal populations in the rat ventromedial thalamic nucleus. The largest population (96%) are thalamo-cortical relay cells which project via the internal capsule to the cerebral cortex. The smaller population of cells (4%) project caudally to the reticular formation and superior colliculus. These two cell types could be distinguished further on the basis of their patterns of spontaneous discharge. Relay cells fluctuate between two activity patterns (i) a rhythmic pattern characterized by periods of high-frequency bursting, and (ii) a more tonic discharge pattern of single spikes. The caudally projecting cells had a characteristic fast, regular type of spontaneous firing. Brachium conjunctivum stimulation evokes two distinct responses in thalamic relay cells, (i) a short-latency single spike, (ii) a longer latency, rhythmic response of 2–3 spikes. Both excitatory responses are followed by a period of cell quiescence. The type of response is dependent upon the cell's firing pattern. The short-latency response occurs during tonic, single-spike activity whilst the longer latency response occurs during highfrequency bursting activity. The short-latency response can be altered to the long latency response by increasing the level of anaesthesia or by applying a conditioning shock to known inhibitory pathways. Conversely the long latency response can be altered to the short-latency response by decreasing anaesthesia or by stimulation of the reticular formation. It is argued that both response types are evoked monosynaptically by activation of the same cerebello-thalamic fibres but that different ionic conductances which are active at different levels of membrane polarization are responsible for the two response patterns. Efficient time-locked cerebellothalamo-cortical transmission occurs only during tonic single-spike activity, when cerebellar stimulation evokes a short-latency response. Such transmission is allowed or disallowed by the fine balance between converging excitatory and inhibitory afferents. In addition to a monosynaptic excitatory input from the cerebellar nuclei, relay cells received converging synaptic inputs from the substantia nigra, cerebral cortex, reticular formation and superior colliculus. Due to the anatomical arrangement in the rat it proved impossible to assess the role of the pallidum. The population of caudally projecting cells also received several converging synaptic inputs, but unlike those influencing relay cells, these inputs were all excitatory. We have obtained no clear physiological evidence for the occurrence of local interneurones within the ventromedial nucleus. However, a powerful recurrent inhibitory circuit is activated following antidromic activation of relay cells. The interneurones responsible for this inhibition appear to lie in the thalamic nucleus reticularis.Abbreviations ACh Acetylcholine - ACG Autocorrelollogram - BC Brachium Conjunctivum - EEG Electroencephalogram - GABA Gamma aminobutyric acid - GP Globus Pallidus - IPSP Inhibitory post-synaptic potential - IC Internal capsule - ISIH Interspike interval histogram - MRF Mesencephalic reticular formation - PSTH Post stimulus time histogram - St Striatum - SN Substantia Nigra - SC Superior Colliculus - VM Ventromedial thalamic nucleus     

Localization of chick retinal 24,000 dalton protein (visinin)-like immunoreactivity in the rat lower brain stem

The distribution of visinin, a 24,000 dalton peptide, in the lower brain stem of the rat was examined by means of an indirect immunofluorescent method. Visinin-immunoreactive structures were found to be unevenly distributed only in the neuronal elements. The following neuronal systems were strongly labeled by the antiserum; the Purkinje cell system, mammillotegmental system, habenulointerpeduncular system, the second layer of the superior colliculus, ventral tegmental area, substantia nigra pars lateralis, area medial to the medial geniculate body, parabrachial area, dorsal and ventral nuclei of the lateral lemniscus, pontine reticular formation just medial to the trigeminal principal nucleus, superior olivary nucleus, solitarii nucleus, external layer of the inferior colliculus and spinal trigeminal nucleus. The densities of the labeled fibers in these areas paralleled those of the labeled cells. In addition, highly dense visinin-immunoreactive fiber plexuses were seen in the zona compacta of the substantia nigra, lateral portion of the interpeduncular nucleus, ventral tegmental nucleus of Gudden and vestibular nucleus.     

Metabolic activity of excitatory parafascicular and pedunculopontine inputs to the subthalamic nucleus in a rat model of Parkinson's disease

Using a combination of metabolic measurement and retrograde tracing, we show that the neurons in the pedunculopontine nucleus and parafascicular nucleus of the thalamus that project to the subthalamic nucleus are hyperactive after nigrostriatal dopaminergic denervation in rats. In Parkinson's disease, the loss of dopaminergic neurons induces a cascade of functional changes in the basal ganglia circuitry including a hyperactivity of the subthalamic nucleus. This hyperactivity is thought to be due to a diminution of the inhibitory pallidal influence. However, recent studies have suggested that other cerebral structures are involved in the subthalamic neuronal hyperactivity. This study was undertaken to identify these cerebral structures. Neurons projecting to the subthalamic nucleus were identified by retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, injected into the subthalamic nucleus of rats with 6-hydroxydopamine unilateral lesion of the substantia nigra pars compacta and sham-lesioned animals. Metabolic activity was determined in the same neurons using in situ hybridization for the first subunit of cytochrome oxidase messenger RNA, a metabolic marker, and image analysis. Horseradish peroxidase-labeled neurons were found in the globus pallidus, parafascicular and pedunculopontine nucleus and sometimes in raphe nuclei and the substantia nigra pars compacta. Measurement of metabolic activity was performed for the globus pallidus, the pedunculopontine and parafascicular nuclei. The expression level of the first subunit of cytochrome oxidase messenger RNA in neurons projecting to the subthalamic nucleus was 62% higher in parafascicular neurons and 123% higher in pedunculopontine neurons in 6-hydroxydopamine-lesioned rats, compared to sham-lesioned animals. An increase was also observed in the globus pallidus, but did not reach significance.Our results suggest that hyperactivity of subthalamic neurons could be due, at least in part, to an increase of excitatory input arising from the pedunculopontine and parafascicular nuclei. These data also suggest that the latter structures may play an important role in the physiopathology of Parkinson's disease.     

Inhibitory nigral influence on cerebellar evoked responses in the rat ventromedial thalamic nucleus

Summary The ventral medial nucleus of the thalamus (VM) has been shown in rats and cats to constitute a common target for nigro- and cerebellothalamic pathways. In the present study the responses of VM neurons to ipsilateral substantia nigra (SN) and contralateral cerebellar nuclei stimulation were analyzed in the rat. The typical response of VM neurons to SN stimulation consisted of a pure short-latency (1.1–3 ms), short-duration (7–17 ms) IPSP. Latencies of these responses were accorded well with the conduction velocity of the nigrothalamic fibers as measured on the basis of antidromic activation of this pathway. A high percentage (58%) of the thalamic neurons receiving the inhibitory nigral effect were also affected by cerebellar stimulation. The cerebellar effect consisted of a short-latency depolarizing potential which could trigger an action potential. These responses were invariably blocked during the course of SN evoked inhibition. Such convergence was found with fastigial as well as interpositus/dentatus evoked responses.The demonstration of an interaction between the processing of SN and cerebellar output at thalamic level provides an important clue for the understanding of the neurophysiologic mechanisms by which SN acts on motor behavior.     

Nucleus tegmenti pedunculopontinus: Efferent connections with special reference to the basal ganglia,studied in the rat by anterograde and retrograde transport of horseradish peroxidase

The efferent connections of the brain stem nucleus tegmenti pedunculopontinus were studied in the rat using the techniques of anterograde and retrograde transport of the enzyme horseradish peroxidase, laying particular emphasis on that part of pedunculopontinus which receives direct descending projections from the basal ganglia and related nuclei. In a preliminary series of experiments horseradish peroxidase was injected into either the entopeduncular nucleus or the subthalamic nucleus and, following anterograde transport of enzyme, terminal labelling was identified in nucleus tegmenti pedunculopontinus, surrounding the brachium conjunctivum in the caudal mesencephalon.In a subsequent series of experiments, horseradish peroxidase was injected into that region of nucleus tegmenti pedunculopontinus which receives entopeduncular and subthalamic efferents and its efferent projections were studied by anterograde transport of the enzyme. The results indicate that nucleus tegmenti pedunculopontinus gives rise to widely distributed efferent projections which terminate rostrally in mesencephalic, diencephalic and telencephalic structures and caudally in the pontine tegmentum. In the mesencephalon, terminal labelling was found in the pars compacta of the ipsilateral substantia nigra and sometimes in the adjoining ventral tegmental area. Labelling was also found in the ipsilateral half of the periaqueductal grey. In the diencephalon terminal labelling occurred bilaterally in the subthalamic nucleus and ipsilaterally in the intralaminar nuclei of the thalamus. Further rostrally, terminal labelling was particularly evident in the ipsilateral pallidal complex, especially in the caudal two-thirds of the entopeduncular nucleus and the ventral half of the caudal third of the globus pallidus. Caudal to pedunculopontine injection sites dense labelling was observed in the reticular formation of the pontine tegmentum.In a final series of experiments, confirmation of apparent pedunculopontine efferent projections was sought using the retrograde transport of horseradish peroxidase. Enzyme was injected into sites possibly receiving pedunculopontine efferents and the peribrachial area of the brain stem was examined for retrograde cell labelling. In this way, pedunculopontine projections were confirmed to the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra, parafascicular nucleus and pontine reticular formation. Injections into the globus pallidus or subthalamic nucleus gave rise to retrograde cell labelling bilaterally in pedunculopontinus. In addition, retrograde transport studies alone demonstrated projections from pedunculopontinus to the cerebral cortex and to the spinal cord.It is concluded that the nucleus tegmenti pedunculopontinus has reciprocal relationships with parts of the basal ganglia and some functionally related nuclei (in particular, the pallidal complex, subthalamic nucleus and substantia nigra). These connections support the view that nucleus tegmenti pedunculopontinus is likely to be involved in the subcortical regulation and mediation of basal ganglia influences upon the lower motor system. This suggests a potential role for pedunculopontine afferent and efferent pathways in the pathophysiology of basal ganglia related disorders of movement.     

Desending and intrinsic inputs to dorsal cochlear nucleus of cats: A horseradish peroxidase study

Horseradish peroxidase was injected unilaterally into the dorsal cochlear nucleus of adult cats in efforts to find neurons innervating the dorsal cochlear nucleus from (1) higher auditory nuclei or (2) other subdivisions of the cochlear nucleus. Following horseradish peroxidase injections and short survival periods, reactive neurons were most common in the dorsal and ventral nuclei of the lateral lemniscus and in the superior olivary complex of both sides of the brain stem. In the superior olivary complex, most neurons of the medial segment and border cells of the lateral segment reacted as did periolivary cells of the ventrolateral, dorsomedial, and preolivary areas, but not in the medial nucleus of the trapezoid body. Hilus neurons of the lateral superior olive reacted contralateral to the injection site. Although inferior colliculus neurons contained lightly stained granules bilaterally, more reactive neurons (including unusually large tripolar neurons) contained heavily stained granules in the contralateral colliculus. Intrinsic reactive neurons mainly included ipsilateral octopus cells, multipolar neurons of the nerve root regions, and stellate cells of the more rostra] anteroventral cochlear nucleus. All findings were confirmed by comparison to control animals.Our findings of specific neuronal types projecting to the cat dorsal cochlear nucleus suggest a relatively greater input from the nuclei of the lateral lemnisci of both sides than previously believed. Also, our results showed an unusually heavy input from the nearby superior olivary complex to the dorsal cochlear nucleus as well as inputs from specific cell types of the ipsilateral antero- and postero-ventral cochlear nucleus. By correlating these findings with those of other types of studies, we concluded that (1) too much emphasis has been placed upon inputs to the dorsal cochlear nucleus from the inferior colliculus relative to the descending pontine inputs and that (2) a new circuit involving the ventral cochlear nucleus, the dorsal cochlear nucleus and the medial superior olive may provide binaural information to large dorsal cochlear nucleus cells that terminate in their own unique areas of higher auditory nuclei.     

Quantitative evaluation of crossed and uncrossed projections from basal ganglia and cerebellum to the cat thalamus

Quantitative and qualitative analysis of crossed vs uncrossed projections from the substantia nigra, entopeduncular nucleus and individual cerebellar nuclei to the thalamus was undertaken in nine adult cats using retrograde labeling with horseradish peroxidase and fluorescent dyes. The results indicate that about 90% of entopeduncular nucleus neurons and 50% of substantia nigra neurons give rise to ipsilateral projections to the thalamus whereas the contralateral component of these projections originates from about 10 and 7% neurons of entopeduncular nucleus and substantia nigra, respectively. Some of the fibers constituting the contralateral component are represented by branching axon collaterals of the neurons projecting ipsilaterally. In the basal ganglia thalamic projection, its minor component (contralateral) targets the ventral anterior and ventral medial nuclei the same as its major component (ipsilateral). However, some preferential distribution of the contralateral projections to the ventral medial nucleus appears to exist. In regard to the cerebellothalamic projections it was found that about 90% of neurons located in the dentate and interpositus nuclei and 50% of neurons in the fastigial nucleus project to the contralateral thalamus while 16% of dentate nucleus neurons and 40% of fastigial nucleus neurons give rise to the ipsilateral cerebellothalamic projections. A considerable number of ipsilateral cerebellothalamic fibers are represented by divergent axon collaterals of the same neurons projecting to the contralateral thalamus. The cerebellothalamic projections from all cerebellar nuclei including the fastigial nucleus are targeted primarily to the ventral lateral nucleus both contra- and ipsilaterally. The ventral medial nucleus receives bilateral input from the fastigial nucleus which originates from about one quarter of the thalamus projecting neurons in this nucleus. Of all other cerebellar nuclei only the dentate nucleus projects to the ventral medial nucleus and this projection is exclusively contralateral.     

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.     

Efferent fibers of the subthalamic nucleus in the monkey. A comparison of the efferent projections of the subthalamic nucleus,substantia nigra and globus pallidus

A study was made to determine the efferent projections of the subthalamic nucleus in the monkey. Because of the impossibility of producing lesions in this nucleus, not involving adjacent structures, lesions were produced by different stereotaxic approaches. Comparisons were made with degeneration resulting from localized lesions in substantia nigra and globus pallidus. Degeneration resulting from these lesions was studied in transverse and sagittal sections stained by the Nauta-Gygax method. Efferent fibers from the subthalamic nucleus pass through the internal capsule into the medial pallidal segment; a few fibers are distributed to the lateral pallidum. Some subthalamic efferent fibers pass to the contralateral globus pallidus via the dorsal supraoptic decussation, but none projection to the thalamus. Nigral efferent fibers project to parts of the ventral anterior (VAmc) and ventral lateral (VLm) thalamic nuclei. The medial pallidal segment gives fibers to: (1) ventral anterior (VA), ventral lateral (VLo) and centromedian (CM) thalamic nuclei, and (2) the pedunculopontine nucleus. The lateral pallidal segment projects exclusively to the subthalamic nucleus. Thalamic projections of the substania nigra and globus pallidus are distinctive. Subthalamic projections to the globus pallidus are more profuse than those of the substantia nigra. The following hypothesis is presented: Subthalamic dyskinesia, due to lesions in the subthalamic nucleus, is a consequence of removal of inhibitory influences acting upon the medial segment of the globus pallidus.     

The mode of nigro-thalamic transmission investigated with intracellular recording in the cat

Postsynaptic potentials evoked by stimulating the substantia nigra (SN) were recorded intracellularly from ipsilateral ventral medial (VM), ventral lateral (VL), and ventral anterior (VA) nuclei of the thalamus in cats anesthetized with sodium pentobarbital. SN stimulation evoked inhibitory postsynaptic potentials (IPSP) at a short latency in VM neurons (mean 1.68 ms, SD 0.23, n = 59). The IPSP were produced monosynaptically because linear regression analysis of latency vs. conduction distance between stimulating and recording sites indicated a synaptic delay of less than 0.6 ms. Conduction velocity for these fibers was calculated to be 4.48 m/s. The spots from which IPSP were produced with the lowest threshold were determined for each of 38 VM neurons. IPSP origins thus determined were distributed in the pars reticulata of the SN (SNr) and in the area where nigro-thalamic fibers run. Neurons which received IPSP from the SNr were distributed in the VM nucleus, ventromedial to the VL nucleus, where fibers from the contralateral brachium conjunctivum terminate. Convergence of nigral and cerebellar impulses was not observed in thalamic neurons sampled in this study. Stimulation of the entopeduncular nucleus (ENT) also produced monosynaptic IPSP in VL-VA neurons. The SNr-related cell group was located ventromedially and caudally to the ENT-related cell group. No convergence of nigral and pallidal influences was observed within thalamic neurons.     

Preservation of the direct and indirect pathways in an in vitro preparation of the mouse basal ganglia

We have developed a slice preparation of the mouse basal ganglia which contains portions of the striatum, external pallidum, subthalamic nucleus and substantia nigra and the neocortex. This basal ganglia slice is unique in preserving functional direct and indirect connections between the striatum and the substantia nigra as well as interconnectivity between the globus pallidus and the subthalamic nucleus. We used fiber tract tracing studies and electrophysiological recordings to demonstrate the full functionality of these pathways. Deposits of 1,1'-dioctadecyl-3,3,3',3'-tetra-methylindocarbocyamine perchlorate in the different basal ganglia resulted in labeled fibers in each of their target nuclei. Confirming these results, electrical stimulation of the different nuclei elicited whole-cell recorded postsynaptic potentials in their target neurons with an appropriate pharmacological profile. Electrical and glutamate activation of the striatum evoked bursts of glutamatergic and GABAergic activities in whole-cell recorded nigral neurons indicating that the direct and indirect pathways are operative in this slice. It also showed that the responses evoked are not due to fibers en passant but to the activation of striatal cell bodies. These findings provide the first direct evidence for a preserved basal ganglia circuitry in vitro and make the basal ganglia slice a suitable preparation for analyzing the activity of the direct and indirect pathways in physiological and pathological conditions.     

Neuronal activity in the substantia nigra in the anaesthetized rat has fractal characteristics. Evidence for firing-code patterns in the basal ganglia

Current models of the basal ganglia assume a firing-rate code for information processing. We have applied five complementary computing methods to assess firing patterns in 188 cells of the substantia nigra in the anaesthetized rat. Fractal firing activity was found in 100% of nigral cells projecting to the superior colliculus, in 51% of cells projecting to the thalamus and in 33% of cells projecting to the pedunculopontine nucleus, but was practically absent in dopaminergic nigrostriatal neurons (3%). The finding of fractal firing patterns may lead to a better understanding of the normal operational mode and pathological manifestations of the basal ganglia.