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Y Smith

Publications and source records attributed to Y Smith.

At least 73 records · Page 4Linked to original sources
PubMed1994

Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey.

The cerebral cortex and the intralaminar thalamic nuclei are the major sources of excitatory glutamatergic afferents to the striatum, whereas the midbrain catecholaminergic neurones provide a dense intrastriatal plexus of dopamine-containing terminals. Evidence from various sources suggests that there is a functional interaction between the glutamate- and dopamine-containing terminals in the striatum. The aim of the present study was to determine the synaptic relationships between cortical or thalamic inputs and the dopaminergic afferents in the sensorimotor territory of the monkey striatum. To address this issue, anterograde tracing in combination with immunocytochemistry for tyrosine hydroxylase (TH) was carried out by light and electron microscopy. Squirrel monkeys received injections of biocytin in the primary motor and somatosensory cortical areas or injections of either Phaseolus vulgaris-leucoagglutinin (PHA-L) or biocytin in the centromedian nucleus (CM) of the thalamus. Sections that included the striatum were processed to visualize the anterograde tracers alone or in combination with TH immunoreactivity. The anterogradely labelled fibres from the cerebral cortex and CM display a band-like pattern and are exclusively confined to the postcommissural region of the putamen, whereas TH-immunoreactive axon terminals are homogeneously distributed throughout the entire extent of the striatum. Electron microscopic analysis revealed that the anterogradely labelled terminals from the cerebral cortex form asymmetric synapses almost exclusively with the heads of dendritic spines. The thalamic terminals also form asymmetric synapses, but in contrast to cortical fibres, predominantly with dendrites (67.4%) and less frequently with spines (32.6%). The TH-immunoreactive boutons are heterogeneous in morphology. The most common type (84% of the total population) forms symmetric synapses; of these the majority is in contact with dendritic shafts (72.1%), less with spines (22.5%) and few with perikarya (5.4%). In sections processed to reveal anterogradely labelled cortical fibres and TH-immunoreactive structures, individual spines of striatal neurones were found to receive convergent synaptic inputs from both cortical and TH-immunoreactive boutons. In contrast, anterogradely labelled thalamic terminals and TH-immunoreactive boutons were never seen to form convergent synaptic contacts on the same postsynaptic structure. These findings suggest that the dopaminergic afferents are located to subserve a more specific modulation of afferent cortical input than afferent thalamic input in the sensorimotor territory of the striatum in primates.

Animals↗
PubMed1994

GABAergic projection from the intercalated cell masses of the amygdala to the basal forebrain in cats.

The intercalated cell masses (ICMs) are dense clusters of small GABAergic cells interposed between the basolateral and centromedial nuclear groups of the amygdala. Until now, the ICMs have been largely ignored in anatomical studies of the amygdaloid complex. Thus, this study was undertaken to identify some of their targets by means of tract-tracing methods combined with immunohistochemical techniques. Wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was injected into numerous cortical areas and dorsal thalamic nuclei, in the anterior commissure and/or stria terminalis nuclei, and in the caudate nucleus, as well as into lateral and preoptic hypothalamic areas. Very few retrogradely labeled cells were seen in the ICMs following these injections. In contrast, massive retrograde labeling was found in the rostral groups of ICMs after WGA-HRP injections involving the substantia innominata and horizontal limb of the diagonal band. Furthermore, these retrogradely labeled intercalated cells were also GABA-immunoreactive. Results of iontophoretic injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) in the rostral ICMs confirmed that they contribute a massive projection to the entire extent of the substantia innominata and horizontal limb of the diagonal band. Electron microscopic observations of ultrathin sections prepared for postembedding GABA or glutamate immunocytochemistry revealed that the ICM terminals labeled with PHA-L displayed GABA, but not glutamate immunoreactivity, and formed symmetric synapses with dendritic profiles. The present findings constitute the first direct demonstration of an amygdalofugal GABAergic projection to the basal forebrain. Considering that the basal forebrain contains a group of cholinergic and GABAergic neurons collectively projecting to the entire cortical mantle, this GABAergic projection of the ICMs could allow the amygdaloid complex to influence the activity of widespread cortical regions to which it is not directly connected, at least in the cat.

Amygdala↗
PubMed1994

Synaptic innervation of neurones in the internal pallidal segment by the subthalamic nucleus and the external pallidum in monkeys.

In order to better understand the way by which the subthalamic nucleus interacts with the globus pallidus to control the output of the basal ganglia, we carried out a series of experiments to investigate the pattern of synaptic innervation of the pallidal neurones by the subthalamic terminals in the squirrel monkey. To address this problem we used the anterograde transport of biocytin. Following injections of biocytin in the subthalamic nucleus, rich plexuses of labelled fibres and varicosities formed bands that lay along the medullary lamina in both segments of the ipsilateral pallidum. At the electron microscopic level, two populations of biocytin-containing terminals were identified in the internal pallidum (GPi). A first group of small to medium-sized terminals (type 1; mean cross-sectional area +/- S.D. = 0.41 +/- 0.04 microns 2) contained round vesicles and formed asymmetric synapses with dendritic shafts (95%) of mixed sizes (maximum diameter ranging from 0.3 to 4.0 microns) and spine-like structures (5%). The second group of terminals (type 2) contained pleiomorphic vesicles, had a larger cross-sectional area (mean +/- S.D. = 0.9 +/- 0.4 micron 2) and formed symmetric synapses predominantly with perikarya (41%) and large dendrites (57%). In some cases, the two types of terminals converged at the level of single GPi neurones. Postembedding immunogold method revealed that the type 2 terminals displayed gamma-aminobutyric acid (GABA) immunoreactivity, whereas the type 1 terminals did not. In the external pallidum (GPe), injections in the subthalamic nucleus labelled both type 1 or type 2 terminals. However, the labelled type 2 boutons were much less abundant in GPe than in GPi. The presence of biocytin-labelled perikarya in GPe and the fact that the type 2 terminals displayed GABA immunoreactivity led us to suspect that these terminals were derived from axons of GPe neurones. In agreement with this hypothesis, injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) in GPe labelled terminals in GPi that displayed the morphological features and a pattern of synaptic organization similar to the type 2 terminals. In conclusion, the results of our study demonstrate that the subthalamopallidal terminals form asymmetric synapses that are distributed along the dendritic tree of GPe and GPi neurones. In contrast, the GPe projection to GPi gives rise to large GABA-containing terminals that form symmetric synapses predominantly with the proximal region of pallidal neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Intra-amygdaloid projections of the lateral nucleus in the cat: PHA-L anterograde labeling combined with postembedding GABA and glutamate immunocytochemistry.

Research on the implication of the amygdala in classical fear conditioning suggests that the central amygdaloid nucleus is the output station of the amygdala for conditioned fear responses, while the lateral nucleus acts as the input nucleus, at least for auditory conditioned stimuli. However, the nature and locus of the plastic changes taking place between these two nuclei are unknown partly because the neurotransmitter(s) used by intra-amygdaloid projections of the lateral nucleus has not been identified. To address this issue in cats, anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L) was combined with postembedding immunocytochemistry for gamma-aminobutyric acid (GABA) and glutamate. Two sectors can be recognized in the lateral nucleus of the cat: a shell located laterally along the external capsule, and a core. Iontophoretic injections of PHA-L in these two sectors revealed that they have nonoverlapping intra-amygdaloid targets with the exception of a common projection to the central lateral nucleus. The core projects mainly to itself and to the basomedial nucleus, whereas the shell contributes a massive projection to the basolateral nucleus. No projection of the lateral nucleus to the central medial nucleus was found. Electron microscopically, PHA-L-labeled axon terminals in the lateral, basomedial, basolateral, and central lateral nuclei as well as in the perirhinal and insular cortices formed asymmetric synapses (100%; n = 289) with dendritic spines (77-100%). Moreover, postembedding immunocytochemistry revealed that PHA-L-labeled axon terminals are immunoreactive for glutamate but not GABA. Since most amygdaloid projections to the brainstem originate in the central medial nucleus, these results suggest that intra-amygdaloid targets of the lateral nucleus are involved in the transmission of auditory conditioned stimuli to the central medial nucleus. Moreover, these findings imply that intra-amygdaloid projections of the lateral nucleus use glutamate but not GABA as a neurotransmitter.

Amygdala↗
PubMed1993

Distribution of GABA immunoreactivity in the amygdaloid complex of the cat.

This study describes the distribution of GABA immunoreactivity in the amygdaloid complex of cats. At the light microscopic level, immunopositive structures consisted of morphologically diverse somata and numerous small punctate elements. The latter accounted for most of the staining at low magnification and, at the electron microscopic level, were found to be axon terminals establishing symmetric synaptic contacts with a variety of postsynaptic profiles. Deep and superficial amygdaloid nuclei could be assigned to one of four groups according to (i) the intensity of immunolabeling they displayed, (ii) their density in reactive somata, and (iii) the size of the immunopositive somata they contained. Intercalated cell masses displayed the highest density of strongly immunoreactive cell bodies and presumed GABAergic terminals. However, electron microscope observations showed that intercalated somata were almost devoid of synaptic contacts. In contrast, central and medial nuclei were characterized by a low density of intensely immunoreactive somata and an elevated concentration for GABAergic terminals which contacted somatic and dendritic profiles. In addition, central and medial nuclei contained numerous neurons displaying low to moderate immunoreactivity. Superficial amygdaloid nuclei and nuclei of the basolateral complex displayed an intermediate density of immunoreactive somata and a low to moderate concentration of presumed terminals. Analysis of the distribution of soma areas within these nuclei revealed that the basolateral complex contains a distinct subpopulation of larger immunoreactive neurons. In light of recent electrophysiological findings, these results suggest that the intra-amygdaloid GABAergic system plays a major role in controlling the synaptic responsiveness and spontaneous activity of amygdaloid neurons.

Amygdala↗
PubMed1993

The intercalated cell masses project to the central and medial nuclei of the amygdala in cats.

In order to study the efferent projections of the intercalated cell masses within the amygdaloid complex, iontophoretic injections of cholera toxin B subunit were performed in several amygdaloid nuclei of the centromedial and basolateral groups in cats. Analysis of the ensuing retrograde labeling revealed that the main intra-amygdaloid targets of the intercalated cell masses are the central and medial nuclei. Most intercalated neurons projecting to the medial nucleus were found in the larger, rostrally located intercalated cell masses. In contrast, the majority of intercalated cells projecting to the central medial and central lateral nuclei were found in the smaller, caudally located intercalated cell masses. In addition, evidence for weaker projections to the basolateral nucleus and other intercalated cell masses was obtained. In light of previous immunohistochemical results showing that GABAergic cells represent the main cell type in the intercalated cell masses, these results imply that the intercalated cell masses constitute an important source of GABAergic input to the centromedial complex. The significance of this finding lies in the fact that the intercalated cell masses are located at the interface between the basolateral nuclear group and the centromedial complex, the main route through which the amygdaloid complex can directly influence hypothalamic and brainstem centers involved in the elaboration of autonomic responses and species-specific emotional behaviors.

Amygdala↗
PubMed1992

The striatum and the globus pallidus send convergent synaptic inputs onto single cells in the entopeduncular nucleus of the rat: a double anterograde labelling study combined with postembedding immunocytochemistry for GABA.

The entopeduncular nucleus is one of the major output stations of the basal ganglia. In order to better understand the role of this structure in information flow through the basal ganglia, experiments have been performed in the rat to examine the chemical nature, morphology, and synaptology of the projections from the globus pallidus and striatum to the entopeduncular nucleus. In order to examine the morphology and synaptology of pallidoentopeduncular terminals and striatoentopeduncular terminals, rats were subjected to a double anterograde labelling study. The globus pallidus was injected with Phaseolus vulgaris-leucoagglutinin (PHA-L), and on the same side of the brain, the striatum was injected with biocytin. The entopeduncular nuclei of these animals were then examined for anterogradely labelled pallidal and striatal terminals. Rich plexuses of PHA-L-labelled pallidal terminals and biocytin-labelled striatal terminals were identified throughout the entopeduncular nucleus. At the electron microscopic level, the pallidal boutons were classified as two types. The majority (Type 1), were large boutons that formed symmetrical synapses with the dendrites and perikarya of neurones in the entopeduncular nucleus. Type 2 PHA-L-labelled terminals were much rarer, slightly smaller, and formed asymmetrical synapses. It is suggested that the Type 2 boutons are not derived from the globus pallidus but from the subthalamic nucleus. The biocytin-labelled terminals from the striatum had the typical morphological features of striatal terminals and formed symmetrical synapses. The distribution of the postsynaptic targets of the pallidal terminals and the striatal terminals differed in that the pallidal terminals preferentially made synaptic contact with the more proximal regions of the neurones in the entopeduncular nucleus, whereas the striatal terminals were located more distally on the dendritic trees. Examination in the electron microscope of areas where there was an overlap of the two sets of anterogradely labelled boutons revealed that terminals from the globus pallidus and the striatum made convergent synaptic contact with the perikarya and dendrites of individual neurones in the entopeduncular nucleus. In order to examine the chemical nature of the input to the entopeduncular nucleus from the globus pallidus and the striatum, ultrathin sections were immunostained by the postembedding method to reveal endogenous GABA. Three classes of GABA-containing terminals were identified; two of them formed symmetrical synapses and one rare type formed asymmetrical synapses. The combination of the GABA immunocytochemistry and anterograde labelling revealed that both the striatal and pallidal afferents that make symmetrical synapses with neurones in the entopeduncular nucleus, including those involved in convergent inputs, are GABAergic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity.

The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium-binding protein calbindin D-28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase). The PHA-L-labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the "sensorimotor" territory of the striatum after CM injections, or in the "associative" striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH-diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH-diaphorase-rich zone in the putamen. The terminal pattern of the CM-striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA-L-labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA-L-labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA-L-labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: 1) Pf-striatal fibers profusely arborize within the matrix compartment of the associative territory, 2) CM-striatal fibers form bands that occupy a subregion of the NADPH-diaphorase-rich zone within the sensorimotor territory, and 3) that both Pf- and CM-striatal projections establish asymmetric synapses with dendrites and spines of medium-sized spiny cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1992

Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey.

The cortex projects heavily to the striatum and makes asymmetrical synaptic contact mainly with the spines of medium-sized densely spiny neurones. The possibility exists that corticostriatal terminals also make synaptic contact with classes of striatal interneurones. The primary objective of the present experiment was to determine whether parvalbumin-immunoreactive neurones, which represent a class of GABAergic interneurones in the striatum, also receive a direct synaptic input from corticostriatal fibres. The anterograde tracer biocytin was injected into the motor and premotor cortices of the squirrel monkey (Saimiri sciureus). Following perfuse-fixation, sections of the striatum were processed histochemically to reveal the transported biocytin using an avidin-biotin-peroxidase complex and diaminobenzidine as the chromogen. They were then immunostained to reveal parvalbumin using benzidine dihydrochloride as the chromogen. In both the light and electron microscopes, the morphological features and the afferent synaptic input of the parvalbumin-immunoreactive neurones were similar to those observed in other species. Similarly, the morphology and postsynaptic targets of the corticostriatal terminals were similar to those described in other species. Light microscopic examination revealed that the anterogradely labelled corticostriatal terminals were often in close apposition to the parvalbumin-positive neurones. At the electron microscopic level the biocytin-positive corticostriatal terminals were found to make asymmetrical synaptic contacts mainly with spines. The parvalbumin-positive neurones were seen to have an invaginated nucleus, extensive cytoplasm and relatively few spines. Parvalbumin-immunoreactive dendrites received a dense synaptic input consisting mainly of asymmetric synapses and only a few symmetric synapses. Biocytin-labelled corticostriatal terminals were often seen in asymmetrical synaptic contact with parvalbumin-immunoreactive dendrites. These results show that GABAergic interneurones identified on the basis of parvalbumin immunoreactivity, in addition to the projection neurones of the striatum, are under the direct influence of the cerebral cortex.

Animals↗
PubMed1992

Synaptic organization of GABAergic inputs from the striatum and the globus pallidus onto neurons in the substantia nigra and retrorubral field which project to the medullary reticular formation.

Anatomical tract-tracing and immunohistochemical techniques involving correlated light and electron microscopy were used to determine whether the descending striatal and pallidal afferents to the substantia nigra pars reticulata converge onto individual neurons projecting to the pontomedullary and medullary reticular formation in the rat. Injections of biocytin into the ventrolateral region of the striatum and Phaseolus vulgaris-leucoagglutinin into the ventrolateral and caudal regions of the globus pallidus led to overlapping anterogradely labelled terminal fields within the dorsolateral substantia nigra pars reticulata. These terminal fields were punctuated by neurons which had been retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into the lateral pontomedullary reticular formation. The anterogradely labelled striatal and pallidal terminals displayed different morphological characteristics; the striatal terminals were small and diffusely distributed throughout the neuropil without any particular neuronal association whereas the pallidal terminals were large and formed pericellular baskets around the perikarya of retrogradely and non-retrogradely labelled nigral neurons. In areas of the substantia nigra where there was an overlap between the two terminal fields, individual retrogradely labelled nigroreticular neurons were found to be apposed by both sets of anterogradely labelled terminals. Electron microscopic analysis revealed that the striatonigral and pallidonigral terminals displayed different ultrastructural features, the striatal terminals were small, contained few mitochondria and formed symmetric synaptic contacts predominantly with the distal dendrites of nigroreticular neurons whereas the pallidal terminals were large, contained numerous mitochondria and formed symmetric synaptic contacts preferentially with perikarya and proximal dendrites of nigroreticular neurons. Post-embedding immunohistochemical staining revealed that both striatonigral and pallidonigral terminals, some which formed synaptic contact with nigroreticular neurons, displayed GABA immunoreactivity. Examination of twelve retrogradely labelled neurons in the electron microscope revealed that all received synaptic inputs from both sets of anterogradely labelled terminals. In addition to the substantia nigra pars reticulata, neurons of the retrorubral field were also retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into pontomedullary reticular formation. These retrorubroreticular neurons were part of a continuum of labelled cells which extended from the dorsolateral substantia nigra pars reticulata caudally into the retrorubral field. When combined with anterograde tracing methods it was found that the retrorubroreticular neurons received synaptic inputs from pallidal terminals which were morphologically similar to the pallidonigral terminals and formed symmetric synapses with the neuronal somata and proximal dendrites. In contrast to nigroreticular neurons, the stratonigral terminals were not seen in contact with retrorubroreticular cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Convergence of synaptic inputs from the striatum and the globus pallidus onto identified nigrocollicular cells in the rat: a double anterograde labelling study.

Two major sources of afferent synaptic inputs to projection neurons in the rat substantia nigra reticulata are the striatum and the globus pallidus. In order to understand better the functional relationships between these two afferents in the control of the activity of nigrofugal neurons, experiments have been performed to test the possibility that single nigrofugal cells receive convergent synaptic inputs from the striatum and the globus pallidus. To address this question we have used two different approaches. First, we have developed a double anterograde labelling technique suitable for both light and electron microscopy and combined this procedure with the retrograde transport of lectin-conjugated horseradish peroxidase in order to retrogradely label the nigrocollicular cells. Second, we have combined the anterograde transport of Phaseolus vulgaris-leucoagglutinin from the globus pallidus and immunocytochemistry for DARPP-32 as a marker for the striatal terminals, with the retrograde transport of lectin-conjugated horseradish peroxidase from the superior colliculus. In the double anterograde labelling experiment, biocytin was injected in the striatum, Phaseolus vulgaris-leucoagglutinin in the globus pallidus and lectin-conjugated horseradish peroxidase in the superior colliculus. Following these injections, rich plexuses of biocytin- and Phaseolus vulgaris-leucoagglutinin-labelled terminals were found in the ventral two-thirds of the substantia nigra. The biocytin-positive terminals (striatonigral) were generally small and formed rich plexuses without any apparent neuronal association whereas the Phaseolus vulgaris-leucoagglutinin-labelled terminals (pallidonigral) were much larger and formed baskets around the perikarya of retrogradely and non retrogradely labelled cells in the substantia nigra reticulata. In areas of the substantia nigra reticulata where the fields of biocytin- and Phaseolus vulgaris-leucoagglutinin-labelled terminals overlapped, the perikarya and the proximal dendrites of retrogradely and non retrogradely labelled cells were found to be apposed by numerous Phaseolus vulgaris-leucoagglutinin-immunoreactive pallidonigral terminals and a few biocytin-labelled striatonigral terminals. In the sections prepared for electron microscopy, the biocytin was localized using 3,3'-diaminobenzidine tetrahydrochloride whereas Phaseolus vulgaris-leucoagglutinin was localized using benzidine dihydrochloride. It was thus possible to distinguish the biocytin- from the Phaseolus vulgaris-leucoagglutinin-labelled terminals in the electron microscope by the texture of the reaction product associated with them.4+ Examination of 231 biocytin-labelled (striatonigral) terminals and 105 Phaseolus vulgaris-leucoagglutinin-immunoreactive (pallidronigral) terminals revealed that the striatonigral terminals were generally small, contained few mitochondria and formed symmetric synapses predominantly with the distal dendrites (77%) and far less frequently with the perikarya (3%) of substantia nigra reticulata cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1990

The GABA and substance P input to dopaminergic neurones in the substantia nigra of the rat.

In order to examine the synaptic input to dopaminergic neurones in the substantia nigra from GABAergic terminals and terminals that contain substance P, double and triple immunocytochemical studies were carried out at the light and electron microscopic levels in the rat. In a first series of experiments sections of the substantia nigra were incubated to reveal axon terminals containing either substance P or glutamate decarboxylase and then incubated to reveal dopaminergic neurones using tyrosine hydroxylase immunocytochemistry. Examination of this material in the light microscope revealed that many substance P- and glutamate decarboxylase-immunoreactive boutons were associated with the dopaminergic cells. In the electron microscope it was found that the perikarya and dendrites of the dopaminergic neurons received symmetrical synaptic input from terminals that displayed immunoreactivity for substance P or glutamate decarboxylase. A small proportion of the substance P-positive boutons formed asymmetrical synapses. In a second series of experiments sections of the substantia nigra were processed by the pre-embedding immunocytochemical technique for tyrosine hydroxylase and then the post-embedding immunogold technique for gamma-aminobutyric acid (GABA). Examination in the electron microscope revealed that the tyrosine hydroxylase-positive neurons received symmetrical synaptic input from many GABA-positive terminals. Quantitative analyses demonstrated that a minimum of 50-70% of all boutons afferent to the dopaminergic neurones display glutamate decarboxylase or GABA immunoreactivity. Triple immunocytochemical studies i.e. pre-embedding immunocytochemistry for tyrosine hydroxylase and substance P, combined with post-embedding immunogold staining for GABA, revealed that some of the substance P-immunoreactive boutons that were in contact with the dopaminergic neurones also displayed GABA immunoreactivity. In a third series of experiments the combination of anterograde transport of lectin-conjugated horseradish peroxidase or biocytin with post-embedding GABA immunocytochemistry demonstrated that at least one of the sources of GABA-containing terminals in the substantia nigra is the striatum. The results of the present study: (1) demonstrate that dopaminergic neurones in the substantia nigra receive symmetrical synaptic input from GABAergic and substance P-containing terminals, (2) show that a proportion of these terminals contain both substance P and GABA and (3) suggest that the major synaptic input to dopaminergic neurones is from GABAergic terminals and that a part of this innervation is derived from the striatum.

Animals↗
PubMed1990

The output neurones and the dopaminergic neurones of the substantia nigra receive a GABA-containing input from the globus pallidus in the rat.

One of the major pathways of information flow through the basal ganglia is the pallidonigrofugal system. In order to better understand this system in the rat, experiments have been performed to study the topography, synaptic organization, and neurotransmitter content of the pallidonigral projection and to determine whether the pallidonigral neurones make direct synaptic contacts with nigrofugal cells. This was achieved by combining the anterograde transport of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) with the retrograde transport of lectin-conjugated horseradish peroxidase (WGA-HRP), postembedding immunocytochemistry for gamma-aminobutyric acid (GABA), and pre-embedding immunocytochemistry for tyrosine hydroxylase (TH). Following injections of PHA-L in different regions of the lateral part of the globus pallidus, a substantial number of immunoreactive fibres and terminals occurred in the ipsilateral substantia nigra reticulata (SNr). The immunoreactive elements were distributed according to a rostral to medial and caudal to lateral topography. Injections that were restricted to the medial tip of the globus pallidus led to the anterograde labeling of a small number of fibres that were sparsely distributed in the SNr. The most characteristic feature of the pallidonigral fibres was the presence of large varicosities that were often grouped to form pericellular baskets. Injections of WGA-HRP in the ventromedial thalamic nucleus, superior colliculus, or midbrain tegmentum, including the pedunculopontine nucleus, showed that the perikarya and primary dendrites of the output cells of the SNr were often surrounded by the large pallidonigral varicosities. The number of varicosities surrounding a single cell varied from 2-12. Electron microscopic analysis showed that the varicosities contained round or slightly pleomorphic vesicles and numerous mitochondria and that they established symmetrical synaptic contacts. Quantitative measurements revealed that the varicosities had a maximum diameter varying from 0.5 to 2.5 microns and a mean cross-sectional area of 0.76 +/- 0.25 microns 2 (N = 237, mean +/- S.D.). The postsynaptic structures of the pallidonigral varicosities included perikarya (48%), large dendrites (38%), and small dendrites (14%). A large proportion of these postsynaptic targets were retrogradely labeled after injection of WGA-HRP in the ventromedial thalamic nucleus, superior colliculus, or midbrain tegmentum. Postembedding immunocytochemistry was used to show that the pallidonigral axons and terminals in contact with nigrofugal neurones displayed GABA immunoreactivity. The use of a double immunocytochemical method revealed, that in addition to the nondopaminergic SNr output neurones, the dendrites and perikarya of the substantia nigra pars compacta (SNc) receive an input from the globus pallidus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method.

The organization of the efferent connections of the subthalamic nucleus was studied in the squirrel monkey (Saimiri sciureus) by using the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer. At the level of the basal forebrain, anterogradely labeled fibers and axon terminals were mostly found in the striatopallidal complex and the substantia innominata. In cases in which the PHA-L injection sites were placed in the central or the lateral third of the subthalamic nucleus, numerous anterogradely labeled fibers were seen to arise from the injection loci and innervate massively the globus pallidus. At pallidal levels the fibers formed bands lying parallel and adjacent to the medullary laminae. The number and the complexity of the topographical organization of these bands varied with the size and the location of the PHA-L injection site. When examined at a higher magnification, the bands of subthalamopallidal fibers appeared as rich plexuses of short axon collaterals with small bulbous enlargements that closely surrounded the cell bodies and primary dendrites of pallidal cells. In contrast, PHA-L injection involving the medial tip of the subthalamic nucleus did not produce bandlike fiber patterns in the globus pallidus. Instead, the labeled fibers formed a diffuse plexus occupying the ventral part of the rostral pole of the globus pallidus as well as the subcommissural pallidal region. The substantia innominata contained a moderate number of labeled fibers and axon terminals following injection of PHA-L in the medial tip of the subthalamic nucleus. A small to moderate number of anterogradely labeled fibers were seen in the putamen after all PHA-L injections. These subthalamostriatal fibers were long, linear, and branched infrequently. At midbrain level the substantia nigra contained a significant number of anterogradely labeled fibers and axon terminals following PHA-L injection in the subthalamic nucleus. The subthalamonigral fibers descended along the ventromedial part of the cerebral peduncle and swept laterally to reach their target. Most of these fibers formed small plexuses along the base of the pars reticulata, whereas a few others ascended along the cell columns of the pars compacta that impinged deeply within the pars reticulata. More caudally in the brainstem, a small number of fibers occurred in the area of the pedunculopontine nucleus and in the periaqueductal gray. These findings indicate that besides its well-known connection with the pallidum, the subthalamic nucleus gives rise to widespread projections to other components of the basal ganglia in primates.

Animals↗
PubMed1990

The dopaminergic nigropallidal projection in primates: distinct cellular origin and relative sparing in MPTP-treated monkeys.

In summary, our findings revealed the existence in primates of a dopaminergic pallidal projection that arises from neurons of the substantia nigra-ventral tegmental area complex and terminates preferentially in the internal pallidum. This projection is largely distinct from the nigrostriatal dopaminergic pathway and appears to be relatively spared in parkinsonian monkeys. Thus, in addition to their potent influence at striatal levels, the midbrain dopaminergic neurons may directly modulate the activity of basal ganglia output neurons at pallidal levels.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Neuronal activity of identified posterior hypothalamic neurons projecting to the brainstem peribrachial area of the cat.

Following horseradish peroxidase injections in the brainstem peribrachial (PB) area, massive retrograde labeling was found in the posterior hypothalamic region. Single-unit recordings posterior hypothalamic neurons with antidromically identified projections to the PB area revealed that these neurons have higher firing rates in waking than in slow-wave sleep and dissimilar discharge patterns as compared with intralaminar thalamic neurons. The results are discussed in the context of reciprocal hypothalamo-brainstem circuits.

Action Potentials↗