Comparative activities of tetanus and botulinum toxins

Using immunohistochemical methods we have studied the distribution of substance P fibers, terminals and perikarya throughout the basal ganglia of baboons and at selected levels of the human brain. Immunoreactivity in the substantia nigra pars reticulata, internal segment of the globus pallidus and ventral pallidum was dense and of a characteristic, “woolly-fiber” morphology. The caudate nucleus and putamen contained sharply circumscribed patches of dense immunoreactivity superimposed on a moderately stained background. The external division of the globus pallidus displayed very little immunoreactivity. Two morphological types of immunoreactive cell bodies were present in the caudate nucleus, putamen and nucleus accumbens, and were clustered within the dense patches. The distribution of immunoreactive perikarya within the striatum differed from that reported for rats, as immunoreactive neurons were distributed evenly throughout the rostrocaudal extent rather than being concentrated in the rostral portions.     

Angiotensin converting enzyme immunohistochemistry in rat brain and pituitary gland: correlation of isozyme type with cellular localization

We have localized angiotensin converting enzyme in rat brain and pituitary gland immunohistochemically with an anti-rat lung angiotensin converting enzyme monoclonal antibody. The distribution of immunoreactive angiotensin converting enzyme is identical with that of binding sites for the angiotensin converting enzyme inhibitor, [3H]captopril. Most intense staining is in the choroid plexus and subfornical organ, with intermediate values in the caudate-putamen, globus pallidus, entopeduncular nucleus, pars reticulata of the substantia nigra, posterior pituitary and anterior pituitary. Lower levels are observed in the supraoptic and paraventricular nuclei of the hypothalamus. Within the basal ganglia angiotensin converting enzyme immunoreactivity is distributed throughout the neuropil; no cell bodies are stained, even after colchicine treatment. The punctate pattern of immunoreactivity in the anterior pituitary corresponds to the distribution of endothelial cells. The posterior pituitary is stained diffusely. Angiotensin converting enzyme is increased by 45% in the posterior lobe after pituitary stalk section, demonstrating that this diffuse staining is associated with pituicytes. Antibody specificity was demonstrated by the immunoaffinity purification of angiotensin converting enzyme to homogeneity from crude tissue extracts using anti-angiotensin converting enzyme antibody and protein A-sepharose. The apparent molecular weight by sodium dodecyl sulfate polyacrylamide gel electrophoresis of lung, choroid plexus and anterior pituitary angiotensin converting enzyme is 175,000. In the substantia nigra and caudate putamen, where angiotensin converting enzyme is localized to neuronal as opposed to epithelial cells, the molecular weight is 165,000. The pituicyte angiotensin converting enzyme of the posterior pituitary is 170,000 daltons.     

Single-cell RT-PCR, in situ hybridization histochemical, and immunohistochemical studies of substance P and enkephalin co-occurrence in striatal projection neurons in rats

Single-cell RT-PCR studies in 3-4-week-old rats have raised the possibility that as many as 20% of striatal projection neurons may be a unique type that contains both substance P (SP) and enkephalin (ENK). We used single-cell RT-PCR, retrograde labeling, in situ hybridization histochemistry, and immunolabeling to characterize the abundance of this cell type, its projection target(s), and any developmental changes in its frequency. We found by RT-PCR that 11% of neurons containing either SP or ENK contained both in 4-week-old rats, while in 4-month-old rats SP/ENK colocalization was only 3%. SP-only neurons tended to co-contain dynorphin and ENK-only neurons neurotensin, while SP/ENK neurons tended to contain dynorphin. Single-cell RT-PCR showed SP/ENK co-occurrence in 4-week-old rats to be no more common among striatal neurons retrogradely labeled from the substantia nigra than among those retrogradely labeled from globus pallidus. Double-label in situ hybridization showed SP/ENK perikarya to be scattered throughout striatum, making up 8% of neurons containing either SP or ENK at 4 weeks, but only 4% at 4 months. Immunolabeling showed that presumptive striatal terminals in globus pallidus externus, globus pallidus internus and substantia nigra pars reticulata that colocalized SP and ENK were scarce. Terminals colocalizing SP and ENK were, however, abundant in the substantia nigra pars compacta. Thus, SP-only and ENK-only neurons make up the vast majority of striatal projection neurons in rats, the frequency of SP/ENK colocalizing striatal neurons is low in adult rats (3-4%), and SP/ENK colocalizing neurons primarily project to SNc but do not appear to be confined to striosomes.     

Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons.

In the infant and adult human basal ganglia, the finding of mRNA exclusively in the striatal medium-sized neurons together with the detection of [3H]CP55,940 binding sites in the caudate-putamen, accumbens, substantia nigra pars reticulata and globus pallidus suggests cannabinoid receptor localization on the striatal intrinsic enkephalinergic and substance P-projecting neurons and on their nigral and pallidal terminals. However, the consistent finding of higher binding in the substantia nigra pars reticulata and medial part of the globus pallidus over its lateral segment suggests cannabinoid receptor enrichment on the striatal substance P neurons which express selectively the dopamine D1 receptor.     

A horseradish peroxidase study of afferent connections of the globus pallidus in Macaca mulatta

Summary The high tonic discharge rates of globus pallidus neurons in awake monkeys suggest that these neurons may receive some potent excitatory input. Because most current electrophysiological evidence suggests that the major described pallidal afferent systems from the neostriatum are primarily inhibitory, we used retrograde transport of horseradish peroxidase (HRP) to identify possible additional sources of pallidal afferent fibers. The appropriate location was determined before HRP injection by mapping the characteristic high frequency discharge of single pallidal units in awake animals. In animals with injections confined to the internal pallidal segment, retrograde label was seen in neurons of the pedunculopontine nucleus, dorsal raphe nucleus, substantia nigra, caudate, putamen, subthalamic nucleus, parafascicular nucleus, zona incerta, medial and lateral subthalamic tegmentum, parabrachial nuclei, and locus coeruleus. An injection involving the external pallidal segment and the putamen as well resulted in additional labeling of cells in centromedian nucleus, pulvinar, and the ventromedial thalamus.Abbreviations AC anterior commissure - CG central grey - CM centromedian nucleus - CN caudate nucleus - DM dorsomedial nucleus - DR dorsal raphe nucleus - DSCP decussation of superior cerebellar peduncle - GPe globus pallidus, external segment - GPi globus pallidus, internal segment - LC locus coeruleus - LL lateral lemniscus - MG medial geniculate nucleus - ML medial lemniscus - NVI abducens nucleus - OT optic tract - Pbl lateral parabrachial nucleus - Pbm medial parabrachial nucleus - Pf parafascicular nucleus - PPN pedunculopontine nucleus - PuO oral pulvinar nucleus - RN red nucleus - SCP superior cerebellar peduncle - SI substantia innominata - SNc substantia nigra, pars compacta - SNr substantia nigra, pars reticulata - STN subthalamic nucleus - TMT mamillothalamic tract - VA ventral anterior nucleus - VLc ventral lateral nucleus, pars caudalis - VLm ventral lateral nucleus, pars medialis - VLo ventral lateral nucleus, pars oralis - VPI ventral posterior inferior nucleus - VPM ventral posterior medial nucleus - VPLc ventral posterior lateral nucleus, pars caudalis - ZI zona incerta     

Direct projections from the central amygdaloid nucleus to the globus pallidus and substantia nigra in the cat.

Employing both anterograde and retrograde axonal tracing, we investigated direct projections from the central amygdaloid nucleus to the basal ganglia in the cat. The anterograde axonal tracing of Phaseolus vulgaris-leucoagglutinin revealed that projection fibers from the central amygdaloid nucleus to the basal ganglia ended in the globus pallidus (the feline homolog to the external segment of the globus pallidus of primates) and substantia nigra. The amygdalopallidal fibers terminated chiefly in the medial most part of the globus pallidus at its caudal level. The amygdalonigral fibers terminated densely in the substantia nigra pars lateralis, and moderately in the dorsolateral part of the substantia nigra pars reticulata; none of them were found to end in the substantia nigra pars compacta. Both of the amygdalopallidal and amygdalonigral projections were ipsilateral. These neuronal connections were confirmed by retrograde axonal tracing of cholera toxin B subunit in the second set of the experiments: The cells of origin of the amygdalopallidal and amygdalonigral projections were located predominantly in the lateral part of the central amygdaloid nucleus, and additionally in the intercalated cell islands of the amygdala. Most of them were of small bipolar or multipolar type. The cells projecting to the globus pallidus were preferentially distributed at the rostral levels of the central nucleus and intercalated cell islands of the amygdaloid complex, while those projecting to the substantia nigra were mainly located at the caudal levels of these amygdaloid subdivisions. In the third set of the experiments, sequential double-antigen immunofluorescence histochemistry for transported cholera toxin B subunit and horseradish peroxidase showed that some single neurons in the lateral part of the central amygdaloid nucleus, particularly at its middle level, issued axon collaterals to both the globus pallidus and substantia nigra pars lateralis. The results of the present study indicate that the central amygdaloid nucleus sends projection fibers to the globus pallidus and substantia nigra possibly to exert a limbic influence upon forebrain motor mechanisms.     

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.     

Distribution of DARPP-32 in the basal ganglia: an electron microscopic study

Summary DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein, has been studied by light and electron microscopical immunocytochemistry in the rat caudatoputamen, globus pallidus and substantia nigra. In the caudatoputamen, DARPP-32 was present in neurons of the medium-sized spiny type. Immunoreactivity for DARPP-32 was present in dendritic spines, dendrites, perikaryal cytoplasm, most but not all nuclei, axons and a small number of axon terminals. Immunoreactive axon terminals in the caudatoputamen formed symmetrical synapses with immunolabelled dendritic shafts or somata. Neurons having indented nuclei were never immunoreactive. In the globus pallidus and substantia nigra pars reticulata, DARPP-32 was present in myelinated and unmyelinated axons and in axon terminals. The labelled axon terminals in these regions formed symmetrical synaptic contacts on unlabelled dendritic shafts or on unlabelled somata. These data suggest that DARPP-32 is present in striatal neurons of the medium-sized spiny type and that these DARPP-32-immunoreactive neurons form symmetrical synapses on target neurons in the globus pallidus and substantia nigra. The presence of DARPP-32 in these striatal neurons and in their axon terminals suggests that DARPP-32 mediates part of the response of medium-size spiny neurons in the striaturn to dopamine D-l receptor activation.     

DARPP-32在大鼠全脑的定位分布

目的 探讨DARPP-32在大鼠全脑的表达分布特点.方法 应用免疫组织化学染色技术对大鼠脑内DARPP-32的表达分布进行观察.结果 免疫组织化学染色结果显示,强阳性的DARPP-32染色大部分分布于基底节区和前嗅皮质区,主要分布在伏隔核、尾壳核及杏仁核复合体的神经元胞体内,以及苍白球、腹侧苍白球、脚间核及黑质网状部的...     

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.     

Distribution of gephyrin in the human brain: an immunohistochemical analysis

Gephyrin is an ubiquitously expressed protein that, in the central nervous system, generates a protein scaffold to anchor inhibitory neurotransmitter receptors in the postsynaptic membrane. It was first identified as a protein component of the glycine receptor complex. Recent studies have demonstrated that gephyrin is colocalized with several subtypes of GABA(A) receptors and is part of postsynaptic GABA(A) receptor clusters. Here, we describe a study of the regional and cellular distribution of gephyrin in the human brain, determined by immunohistochemical localisation at the light and confocal laser scanning microscopic levels. At the regional level, gephyrin immunoreactivity was observed in most of the major brain regions examined. The most intense staining was in the cerebral cortex, hippocampus and caudate-putamen, in various brainstem nuclei with more moderate levels in the thalamus and cerebellum. At the cellular level gephyrin immunoreactivity was present on the plasma membranes of the soma and dendrites of pyramidal neurons throughout the various cortical regions examined. In the hippocampus, intense staining was observed on the granule cells of the dentate gyrus, and neurons of the CA1 and CA3 regions showed intense punctate gephyrin staining on their apical dendrites and cell bodies. Gephyrin immunoreactivity was also observed on neurons in the thalamus, globus pallidus and substantia nigra. In the putamen intense labelling of the striosomes was observed; most of the medium-sized neurons in the caudate-putamen were weakly labelled and many large neurons of the striatum were conspicuously stained. Many of the brainstem nuclei, notably the dorsal motor nucleus of the vagus, hypoglossal nucleus, trigeminal nucleus and inferior olive were all labelled with gephyrin. The spinal cord also showed high levels of gephyrin immunoreactivity. Our results demonstrate that the anchoring protein gephyrin is ubiquitously present in the human brain. We therefore suggest that gephyrin may have a central organizer role in assembling and stabilizing inhibitory postsynaptic membranes in human brain and is similar in function to those observed in the rodent brain. These findings contribute towards elucidating the role of gephyrin in the human brain.     

Correlation between met-enkephalin and substance P immunoreactivity in the primate globus pallidus

Using immunohistochemical techniques, the distribution of enkephalin and substance P immunoreactive fibers and terminals was studied in the globus pallidus of the non-human primate. In the external segment of the globus pallidus, enkephalin immunoreactivity was very dense while only sparse to moderate substance P staining was observed. Enkephalin immunoreactivity in the inner portion of the internal segment was moderate while such fibers were sparse in the outer portion of the internal segment. Substance P immunoreactivity was dense throughout the internal segment of the globus pallidus.The pattern of enkephalin and substance P immunoreactivity in the globus pallidus of the non-human primate as reported in the present study is of interest with regard to pallidal efferents. The pallidosubthalmic projection, arising from the external segment of the globus pallidus, is likely to be strongly influenced by the very dense network of enkephalin immunoreactive fibers and terminals in this region. Conversely, substance P immunoreactive elements are sparse in the external segment, and are, therefore, unlikely to influence significantly activity carried by the pallidosubthalmic projection. Since the inner portion of the internal segment contains moderate enkephalin immunoreactivity and dense substance P immunoreactivity, the information carried by the lenticular fasiculus may be modulated by both of these putative transmitters. On the other hand, based on the densities of immunoreactivity, the ansa lenticularis, which arises from the outer portion of the internal segment, is likely to be under greater influence of the dense substance P projection to this area.     

Dizocilpine maleate, MK-801, but not 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline, NBQX, prevents transneuronal degeneration of nigral neurons after neurotoxic striatal-pallidal lesion

Unilateral neurotoxin lesion of rat caudate-putamen and globus pallidus resulted in delayed, transneuronal degeneration of GABAergic substantia nigra pars reticulata neurons. To explore whether the disinhibition of endogenous glutamate excitatory input played a role in the degeneration of substantia nigra pars reticulata neurons, animals with unilateral striatal-pallidal lesions received three daily intraperitoneal injections of either dizocilpine maleate (MK-801, 1 or 10 mg/kg), an N-methyl-D-aspartate glutamate receptor blocker, or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX, 30 mg/kg), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor blocker, that began 24 h after the striatal-pallidal neurotoxin lesion. Drug treatment affected neither the volume of the initial lesion nor the volume of striatal-pallidal glial fibrillary acidic protein immunoreactivity. Neuron number in the substantia nigra pars reticulata ipsilateral to the lesioned striatopallidum was reduced on average by 37% in untreated control rats, in low dose MK-801, and NBQX-treated rats (P<0.0001). However, in animals treated with high doses of MK-801 there was no difference in the number of neurons in the substantia nigra pars reticulata ipsilateral or contralateral to the neurotoxin lesion. These data demonstrate that dose-related treatment with N-methyl-D-aspartate glutamate receptor blockers protects substantia nigra pars reticulata neurons, and suggests that glutamatergic mechanisms play a role in delayed transneuronal degeneration.     

Survival and growth of neurons with enkephalin-like immunoreactivity in fetal brain areas grafted to the anterior chamber of the eye

Areas of fetal rat brain and spinal cord known to contain enkephalin-like immunoreactive cell bodies and/or terminal fields were transplanted to the anterior chamber of the eye of adult rats. Enkephalin-like immunoreactive neurons survive and produce an enkephalin-like immunoreactive fiber network within grafts of spinal cord, ventral medulla oblongata, ventrolateral pons, tectum, locus coeruleus, substantia nigra and the areas containing columna fornicis and globus pallidus. Although single intraocular grafts of neocortex do not apparently contain enkephalin-like immunoreactive fibers, such grafts contain a variable amount of sparsely distributed enkephalin-like fibers when sequentially grafted in oculo with either locus coeruleus or spinal cord. Combinations of locus coeruleus and globus pallidus contained a rich enkephalin fiber network in the locus coeruleus part and a sparse innervation of the globus pallidus part.

We conclude that enkephalin-like immunoreactive neurons in small areas of fetal rat brain can be successfully transplanted to the anterior chamber of the eye. They are able to survive and develop to maturity in complete isolation from the rest of the brain. In general, the enkephalin-like immunoreactive fiber density in the various single grafts approximated that of their brain counterparts in situ. Fiber formation can be reinitiated in mature enkephalin-like immunoreactive neurons by addition of new brain target areas. Thus, the technique permits establishment of isolated, defined enkephalin systems and pathways accessible to functional analysis.     

Immunohistochemical localization of cytochrome P-450 in rat brain

The presence of cytochrome P-450 in rat brain was studied by immunohistochemistry, using antibodies to cytochrome P-450 purified from livers of phenobarbital- or 3-methylcholanthrene-treated rats. Immunoreactive nerves were observed only in brain sections incubated with immunoglobulin-G to 3-methylcholanthrene-induced cytochrome P-450. This immunoreactivity was abolished by preabsorption of the antibody with highly purified rat liver cytochrome P-450c, the major cytochrome P-450 isozyme induced by 3-methylcholanthrene, but was not affected by other cytochrome P-450 isozymes induced by phenobarbital, isosafrole or pregnenolone-16-carbonitrile.

The most abundant concentration of nerve fibers with cytochrome P-450 immunoreactivity was observed in the globus pallidus. Immunoreactive fibers were also observed in the caudate putamen, amygdala, septum, ventromedial nucleus of the hypothalamus, medial forebrain bundle, ansa lenticularis, and ventromedial portion of the internal capsule and crus cerebri. Cell bodies with cytochrome P-450 immunoreactivity were observed in the caudate putamen and in the perifornical area of the hypothalamus. The cytochrome P-450 immunoreactive fibers in the globus pallidus and caudate putamen do not appear to emanate from cell bodies in the substantia nigra, since there was no reduction in the density of these fibers after unilateral stereotaxic electrolytic destruction of the substantia nigra (zona compacta and reticulata). Our data suggest that these striatal nerve processes are derived from cell bodies within the caudate putamen itself.

The present results indicate that rat brain contains a form of cytochrome P-450 with antigenic relatedness to the hepatic 3-methylcholanthrene-inducible cytochrome P-450c. This cytochrome P-450 isozyme was detected in brain areas which metabolize morphine and convert estradiol and estrone into catecholestrogens, which suggests an important role for this enzyme in the metabolism of both ex´ogenous and endogenous compounds in brain.     

Distribution of divalent metal transporter-1 in the monkey basal ganglia

An accumulation of iron occurs in the brain with age, and it is thought that this may contribute to the pathology of certain neurodegenerative diseases, including Parkinson's disease. In this study, we elucidated the distribution of divalent metal transporter-1 (DMT1) in the monkey basal ganglia by immunocytochemistry, and compared it with the distribution of ferrous iron in these nuclei by Turnbull's Blue histochemical staining. We observed a general correlation between levels of DMT1, and iron staining. Thus, regions such as the caudate nucleus, putamen, and substantia nigra pars reticulata contained dense staining of DMT1 in astrocytic processes, and were also observed to contain large numbers of ferrous iron granules. The exceptions were the globus pallidus externa and interna, which contained light DMT1 staining, but large numbers of ferrous iron granules. The thalamus, subthalamic nucleus, and substantia nigra pars compacta contained neurons that were lightly stained for DMT1, but few or no iron granules. The high levels of DMT1 expression in some of the nuclei of the basal ganglia, particularly the caudate nucleus, putamen, and substantia nigra pars reticulata, may account for the high levels of iron in these regions.     

Peptidase-containing neurons in rat striatum

The effects of surgical lesions on peptidase activity have been studied in the striatonigral system of the rat brain. Knife cuts separating the anterior part of the caudate putamen from the globus pallidus resulted in a decrease in the activity of angiotensin-converting enzyme and alanyl aminopeptidase in both the globus pallidus and substantia nigra. The activity of nigral prolyl endopeptidase and leucyl aminopeptidase was also decreased. An increase in dipeptidyl aminopeptidase and arginyl endopeptidase activity was observed in both the caudate putamen and globus pallidus. These results suggest that the striatal neurons containing angiotensin-converting enzyme or alanyl aminopeptidase project to both the globus pallidus and substantia nigra, and the neurons containing prolyl endopeptidase and/or leucyl aminopeptidase project to the substantia nigra. Dipeptidyl aminopeptidase and arginyl endopeptidase are probably associated with glial function.     

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.     

Pallidotectal projection to the inferior colliculus of the rat

Summary After injection of fluorescent tracer into the inferior colliculus (IC), retrogradely labeled cells were observed not only in the temporoauditory cortex (ACx) and the substantia nigra pars lateralis, but also in the globus pallidus (GP). These labeled GP cells were localized exclusively in the caudal portion of the GP, which has been known to project to the ACx. Employing a retrograde fluorescent double labeling technique, the GP-IC neurons were found to be distributed in a separate manner from the GP-ACx neurons within the caudal GP. The present study provides further anatomical evidence that the caudal GP has a functional role in auditory processing.Abbreviations ACx temporoauditory cortex - BC Brachium conjunctivum - CP cerebral peduncle - CPu caudate putamen - DY Diamidino Yellow - EP entopeduncular nucleus - FG Fluoro-Gold - GP globus pallidus - I internal capsule - IC inferior colliculus - OT optic tract - SC superior colliculus - SN1 substantia nigra pars lateralis - T thalamus - TB True Blue - TPC nucleus tegmenti pedunculopontinus pars compacta     

GABAergic control of rat substantia nigra dopaminergic neurons: role of globus pallidus and substantia nigra pars reticulata

Dopaminergic neurons in vivo fire spontaneously in three distinct patterns or modes. It has previously been shown that the firing pattern of substantia nigra dopaminergic neurons can be differentially modulated by local application of GABA(A) and GABA(B) receptor antagonists. The GABA(A) antagonists, bicuculline or picrotoxin, greatly increase burst firing in dopaminergic neurons whereas GABA(B) antagonists cause a modest shift away from burst firing towards pacemaker-like firing. The three principal GABAergic inputs to nigral dopaminergic neurons arise from striatum, globus pallidus and from the axon collaterals of nigral pars reticulata projection neurons, each of which appear to act in vivo primarily on GABA(A) receptors (see preceding paper). In this study we attempted to determine on which afferent pathway(s) GABA(A) antagonists were acting to cause burst firing. Substantia nigra dopaminergic neurons were studied by single unit extracellular recordings in urethane anesthetized rats during pharmacologically induced inhibition and excitation of globus pallidus. Muscimol-induced inhibition of pallidal neurons produced an increase in the regularity of firing of nigral dopaminergic neurons together with a slight decrease in firing rate. Bicuculline-induced excitation of globus pallidus neurons produced a marked increase in burst firing together with a modest increase in firing rate. These changes in firing rate were in the opposite direction to what would be expected for a monosynaptic GABAergic pallidonigral input. Examination of the response of pars reticulata GABAergic neurons to similar manipulations of globus pallidus revealed that the firing rates of these neurons were much more sensitive to changes in globus pallidus neuron firing rate than dopaminergic neurons and that they responded in the opposite direction. Pallidal inhibition produced a dramatic increase in the firing rate of pars reticulata GABAergic neurons while pallidal excitation suppressed the spontaneous activity of pars reticulata GABAergic neurons. These data suggest that globus pallidus exerts significant control over the firing rate and pattern of substantia nigra dopaminergic neurons through a disynaptic pathway involving nigral pars reticulata GABAergic neurons and that at least one important way in which local application of bicuculline induces burst firing of dopaminergic neurons is by disinhibition of this tonic inhibitory input.