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J P Bolam

Publications and source records attributed to J P Bolam.

At least 19 recordsLinked to original sources
PubMed1997

Efferent connections of the internal globus pallidus in the squirrel monkey: I. Topography and synaptic organization of the pallidothalamic projection.

The objectives of this study were, on one hand, to better understand how the segregated functional pathways from the cerebral cortex through the striatopallidal complex emerged in the projections to the thalamus and, on the other hand, to compare the ultrastructure and synaptic organization of the pallidal efferents to the ventrolateral (VL) and centromedian (CM) thalamic nuclei in primates. These aims were achieved by injections of the retrograde-anterograde tracer, biotinylated dextran amine (BDA), in different functional regions of the internal pallidum (GPi) in squirrel monkeys. The location of retrogradely labelled cells in the striatum was determined to ascertain the functional specificity of the injection sites. Injections in the ventrolateral two-thirds of the GPi (group 1) led to retrograde labelling in the postcommissural region of the putamen ("sensorimotor striatum") and plexuses of labelled fibers in the rostral one-third of the principal ventrolateral nucleus (VLp) and the central part of the CM. On the other hand, injections in the dorsal one-third (group 3) and the rostromedial pole (group 4) of the GPi led to retrogradely labelled cells in the body of the caudate nucleus ("associative striatum") and the ventral striatum ("limbic striatum"), respectively. After those injections, dense plexuses of anterogradely labelled varicosities were found in common thalamic nuclei, including the parvocellular ventral anterior nucleus (VApc), the dorsal VL (VLd), and the rostrodorsal part of the parafascicular nucleus (PF). In the caudal two-thirds of the CM/PF, the labelled fibers formed a band that lay along the dorsal border of the complex in a region called the dorsolateral PF (PFdl) in this study. The ventromedial nucleus (VM) was densely labelled only after injections in the rostromedial GPi, whereas the dorsal part of the zona incerta was labelled in both groups. At the electron microscopic level, the BDA-positive terminals in the VLp were larger and more elongated than those in the CM but, overall, displayed the same pattern of synaptic organization. Our findings indicate 1) that some associative and limbic cortical information, which is largely processed in segregated corticostriatopallidal channels, converges to common thalamic nuclei and 2) that the PF is a major target of associative and limbic GPi efferents in monkeys.

Animals↗
PubMed1997

Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat.

Glutamate released in the basal ganglia is involved in the expression of clinical symptoms of neurodegenerative diseases like Parkinson's or Huntington's. Neostriatal neurons are the targets of glutamatergic inputs derived from the cortex and the thalamus acting via AMPA-type as well as other glutamate receptors. To determine the location of subunits of the AMPA subclass of glutamate receptors (GluR) in the rat neostriatum, we applied multiple immunocytochemical techniques using anti-peptide antibodies against the GluR1, GluR2/3, and GluR4 subunits at both the light and electron microscopic levels. All medium spiny efferent neurons, some of which were identified as striatonigral neurons, displayed immunoreactivity for GluR1 and GluR2/3 subunits. Double immunofluorescence revealed that at least 70-90% of parvalbumin-immunopositive GABAergic interneurons were immunoreactive for each of GluR1, GluR2/3, or GluR4 subunits and that at least 40% of choline acetyltransferase-immunopositive cholinergic interneurons were immunopositive for GluR1 or GluR4 subunits. The majority of nitric oxide synthase-immunopositive neurons had no detectable immunoreactivity for any of the AMPA receptor subunits. Electron microscopic analysis confirmed the presence of immunoreactivity for GluR1 and GluR2/3 in the perikarya of spiny neurons and interneurons and GluR4 in perikarya of interneurons only. GluR1 and GluR2/3 subunits were detected in dendrites and spines. A significant population of extrasynaptic receptors was revealed by pre-embedding immunogold labeling along the plasma membranes of perikarya, dendrites, and spines. Receptors were concentrated in the postsynaptic membrane specialization of asymmetrical synapses, as revealed by the postembedding immunogold method. Quantitative analysis demonstrated that immunoreactivity for the GluR1 and GluR2/3 subunits is higher at the periphery than at the middle of the postsynaptic membrane specialization. Our results demonstrate that AMPA receptor subunits are distributed widely and heterogeneously among striatal neurons and are concentrated on the postsynaptic membrane of asymmetrical synaptic specializations, although extrasynaptic receptors are also present.

Animals↗
PubMed1997

Synaptic integration of functionally diverse pallidal information in the entopeduncular nucleus and subthalamic nucleus in the rat.

To determine the principles of synaptic innervation of neurons in the entopeduncular nucleus and subthalamic nucleus by neurons of functionally distinct regions of the pallidal complex, double anterograde labeling was carried out at both light and electron microscopic levels in the rat. Deposits of the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine were placed in different functional domains of the pallidal complex in the same animals. The tracer deposits in the ventral pallidum and the globus pallidus gave rise to GABA-immunopositive projections to the entopeduncular nucleus, the subthalamic nucleus, and the more medial lateral hypothalamus that were largely segregated but overlapped at the interface between the two fields of projection. In these regions the proximal parts of individual neurons in the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus received synaptic input from terminals derived from both the ventral pallidum and the globus pallidus. Furthermore, the analysis of the afferent synaptic input to the dendrites of neurons in the subthalamic nucleus that cross functional boundaries of the nucleus defined by the pallidal inputs, revealed that terminals with the morphological and neurochemical characteristics of those derived from the pallidal complex make synaptic contact with all parts of the dendritic tree, including distal regions. It is concluded that functionally diverse information carried by the descending projections of the pallidal complex is synaptically integrated by neurons of the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus by two mechanisms. First, neurons located at the interface between functionally distinct, but topographically adjacent, projections could integrate diverse information by means of the synaptic convergence at the level of the cell body and proximal dendrites. Second, because the distal dendrites of neurons in the subthalamic nucleus receive input from the pallidum, those that extend across two distinct domains of pallidal input could also provide the morphological basis of integration.

Afferent Pathways↗
PubMed1997

Quantitative and morphometric data indicate precise cellular interactions between serotonin terminals and postsynaptic targets in rat substantia nigra.

We have quantified the density of serotonin axonal varicosities, their synaptic incidence and their distribution among potential targets in the pars reticulata and pars compacta of the rat substantia nigra. Serotonin axonal varicosities, counted at the light microscopic level following in vitro [3H]serotonin uptake and autoradiography, amounted to 9 x 10(6)/mm3 in the pars reticulata and 6 x 10(6)/mm3 in the pars compacta, among the densest serotonin innervations in brain. As determined at the electron microscopic level following immunolabelling for serotonin, virtually all serotonin varicosities in the pars reticulata and 50% of those in the pars compacta formed a synapse, essentially with dendrites. The combination of serotonin immunocytochemistry with tyrosine hydroxylase immunolabelling of dopamine neurons reveals that 20% of the serotonin synaptic contacts in the pars reticulata are on dopamine dendrites and 6% are on a type of unlabelled dendrite characterized by its peculiarly high cytoplasmic content of microtubules. The comparison of the diameter of the dendritic profiles that were in synaptic contact with serotonin-immunoreactive varicosities with the diameter of all other dendritic profiles of the same type suggests that serotoninergic varicosities innervate dopamine dendrites uniformly along their length, whereas they tend to contact microtubule-filled dendrites in more proximal regions and the other, unidentified dendrites in more distal regions. Furthermore, the size of the serotonin-immunoreactive varicosities and of their synaptic junctions is significantly smaller on dopamine dendrites and larger on microtubule-filled dendrites than on other, unidentified dendrites, indicating that the nature of the postsynaptic target is an important determinant of synaptic dimensions. These data should help to clarify the role of serotonin in the nigral control of motor functions. They indicate that this dense serotonin input to the substantia nigra is very precisely organized, acting through both "non-junctional" and "junctional" modes of neurotransmission in the pars compacta, which projects to the neostriatum and the limbic system, whereas the predominant mode of serotonin transmission appears to be of the "junctional" type in the pars reticulata, where serotonin can finely control the motor output of the basal ganglia by acting on the GABA projection neurons either directly or through the local release of dopamine by dopaminergic dendrites. The data also raise the possibility that the postsynaptic targets have trophic retrograde influences on serotoninergic terminals.

Animals↗
PubMed1996

The subthalamic nucleus and the external pallidum: two tightly interconnected structures that control the output of the basal ganglia in the monkey.

The aim of the present study was to elucidate the organization of the interconnections between the subthalamic nucleus and the two segments of the globus pallidus in squirrel monkeys. By making small deposits of tracers in the two segments of the globus pallidus, we demonstrate that interconnected neurons of the subthalamic nucleus and the external pallidum innervate, via axon collaterals, the same population of neurons in the internal pallidum. Furthermore, this organizational principle holds true for different functional regions of the pallidum and the subthalamic nucleus. Injections of biotinylated dextran amine were made in the dorsal (associative), ventrolateral (sensorimotor) and rostromedial (limbic) regions of the internal pallidum. Following these injections, there were rich clusters of labelled terminals in register with retrogradely labelled perikarya in related functional regions of the subthalamic nucleus and the external pallidum. At the electron microscopic level, the majority of labelled terminals in the external pallidum displayed the ultrastructural features of boutons from the subthalamic nucleus and were non-immunoreactive for GABA, whereas those in the subthalamic nucleus resembled terminals from the external pallidum and displayed GABA immunoreactivity. In both cases, the synaptic targets of the labelled terminals included labelled neurons. These observations suggest that the biotinylated dextran amine injected in the internal globus pallidus was transported retrogradely to perikarya in the external pallidum and the subthalamic nucleus and then anterogradely, via axon collaterals, to the subthalamic nucleus and the external pallidum respectively. This suggestion was supported by injections of biotinylated dextran amine or Phaseolus vulgaris-leucoagglutinin in regions of the external pallidum that corresponded to those containing retrogradely labelled cells following injections in the internal pallidum. The clusters of labelled cells and varicosities that resulted from these injections were found in regions of the subthalamic nucleus similar to those labelled following injections in the internal globus pallidus. Furthermore, terminals from the external pallidum and the subthalamic nucleus converged on the same regions in the internal globus pallidus. The results of the present tracing study define the basic network underlying the interconnections between the external segment of the globus pallidus and the subthalamic nucleus, and their connections with the output neurons of the basal ganglia in primates.

Animals↗
PubMed1996

The substantia nigra as a site of synaptic integration of functionally diverse information arising from the ventral pallidum and the globus pallidus in the rat.

Voluntary behaviour in mammals requires the integration of information from different parts of the cerebral cortex, notably the limbic, associative and sensorimotor areas, in a neural network that eventually controls the muscles. One region of the brain that has been proposed to subserve such a function are the basal ganglia which receive inputs from all cortical areas. Although information from different cortical areas passes through the basal ganglia as a series of separate parallel pathways there are several sites where integration of the diverse information could occur. In this study we the identify a neural network at the synaptic level that may underlie a powerful mechanism for the integration, within the basal ganglia, of the diverse types of information arising from the cortex. By double anterograde tracing and immunocytochemistry at both the light and electron microscopic levels, we show that individual neurons in the substantia nigra pars reticulata and dopaminergic neurons in the pars compacta each receive multiple GABAergic synaptic inputs both from neurons in the ventral pallidum (which receive input from limbic areas via the nucleus accumbens) and from neurons in the globus pallidus (which receive input from associative and sensorimotor cortices via the neostriatum). Thus, information subserving functions such as emotion, motivation, cognition and movement converges onto basal ganglia output neurons, leading eventually to the muscles, and also on to the dopaminergic neurons which themselves subserve an integrative role by modulating the flow of information from the cortex through the basal ganglia at the level of the neostriatum and nucleus accumbens.

Animals↗
PubMed1996

Synaptic connections between spiny neurons of the direct and indirect pathways in the neostriatum of the rat: evidence from dopamine receptor and neuropeptide immunostaining.

UNLABELLED: The flow of cortical information through the basal ganglia occurs through the so-called 'direct pathway' and 'indirect pathways'. The object of the present work was to attempt to determine whether spiny neurons in the neostriatum that give rise to the direct pathway (i.e. the striatonigral/entopeduncular pathway) and those giving rise to the indirect pathways (i.e. striatopallidal pathway) are synaptically interconnected. The approach was to carry out double immunocytochemistry at the electron microscopic level using antibodies against peptides or dopamine receptor subtypes that are selectively associated with the neurons that give rise to the direct (substance P or D1 receptors) and indirect pathways (enkephalin or D2 receptors). Sections of perfuse-fixed rat neostriatum were immunostained to reveal both substance P immunoreactivity and D2 receptor immunoreactivity or enkephalin and D1 receptor immunoreactivity, respectively. Double peroxidase methods were employed using different chromogens that were distinguishable at both the light and electron microscopic levels. In the electron microscope substance P-immunoreactive terminals were seen in synaptic contact with dendritic structures that displayed immunoreactivity for D2 receptor. Similarly, enkephalin-immunoreactive terminals were seen in synaptic contact with D1-immunoreactive dendritic structures. Thus, axon collaterals of neurons giving rise to the direct pathway form synaptic contacts with neurons that give rise to the indirect pathway and axon collaterals of neurons giving rise to the indirect pathway form synaptic contact with neurons that give rise to the direct pathway. These results indicate that the two pathways of information flow through the basal ganglia are synaptically linked at the level of the neostriatum. KEYWORDS: spiny neurons, direct pathway,indirect pathways, rat neostriatum

Animals↗
PubMed1996

Glutamate-enriched inputs from the mesopontine tegmentum to the entopeduncular nucleus in the rat.

In order to clarify the origin and to examine the synaptology of the projection from the mesopontine tegmentum to the entopeduncular nucleus, rats received discrete deposits of anterograde tracers in different regions of the mesopontine tegmentum. Anterogradely labelled fibres in the entopeduncular nucleus were analysed at the light and electron microscopic levels. To determine the neurochemistry of the projection, the distributions of GABA and glutamate immunoreactivity in anterogradely labelled boutons in the entopenducular nucleus were studied by postembedding immunocytochemistry. The morphological characteristics of anterogradely labelled structures were compared to those of choline acetyltransferase-immunopositive structures. The anterograde tracing demonstrated that the projection to the entopeduncular nucleus arises from the area defined by the cholinergic neurons of the pedunculopontine region and from the more medial and largely non-cholinergic, midbrain extrapyramidal area. The anterogradely labelled terminals formed asymmetrical synaptic contacts with dendritic shafts, cell bodies and more rarely spines in the entopeduncular nucleus, and they were significantly enriched in glutamate immunoreactivity compared to identified GABAergic terminals in the same region. The morphology, trajectory and synaptology of the anterogradely labelled fibres showed similarities to those of choline acetyltransferase-immunopositive fibres and terminals, providing indirect evidence in support of previous suggestions that at least part of the projection is cholinergic. The structures postsynaptic to the anterogradely labelled boutons also received input from other classes of terminals that had the morphological and neurochemical characteristics of boutons derived from the neostriatum, globus pallidus and subthalamic nucleus. These findings imply that the mesopontine tegmentum sends a projection to the entopeduncular nucleus that is heterogeneous with respect to its origin and also possibly its neurochemistry. The synaptology of the projection underlies one route through which the mesopontine tegmentum can exert effects on movement by modulating the direct and indirect pathways of information flow through the basal ganglia.

Animals↗
PubMed1995

The glutamate-enriched cortical and thalamic input to neurons in the subthalamic nucleus of the rat: convergence with GABA-positive terminals.

Neurons of the subthalamic nucleus play a key role in the normal physiology and the pathophysiology of the basal ganglia. In order to understand better how the activity of subthalamic neurons and hence the output of the basal ganglia are controlled, we have reexamined the topography and examined in detail the synaptology and neurochemical nature of the two major excitatory projections to the subthalamic nucleus, that from the cortex and from the parafascicular nucleus of the thalamus. The approach was to use anterograde neuronal tracing and postembedding immunocytochemistry for amino acid transmitters. In confirmation of previous findings the cortical and thalamic projections were topographically organized, although the topography was more finely organized, and the projections more extensive, than previously demonstrated. Cortical and thalamic terminals made asymmetrical synaptic contacts with the dendrites and spines of subthalamic neurons. The thalamic terminals contacted larger postsynaptic targets, and therefore presumably more proximal regions of subthalamic neurons, than did the cortical terminals. Quantitative analysis of the postembedding immunolabelled sections revealed that the cortical and thalamic terminals were significantly enriched in glutamate-immunoreactivity when compared to identified gamma-aminobutyric acid (GABA)-positive terminals, supporting physiological studies that suggest that these projections use glutamate as their neurotransmitter. In addition a small population of nonanterogradely labelled terminals that formed asymmetrical synapses and were immunopositive for GABA were identified. A larger population of terminals that formed symmetrical synapses were also immunopositive for GABA and were probably derived from the globus pallidus. The latter type of terminal was found to make convergent synaptic input with cortical or thalamic terminals on the dendrites and spines of subthalamic neurons, indicating that the "indirect pathways" by which information flows through the basal ganglia converge at the level of individual neurons in the subthalamic nucleus.

Animals↗
PubMed1995

Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy.

The modulatory actions of dopamine on the flow of cortical information through the basal ganglia are mediated mainly through two subtypes of receptors, the D1 and D2 receptors. In order to examine the precise cellular and subcellular location of these receptors, immunocytochemistry using subtype specific antibodies was performed on sections of rat basal ganglia at both the light and electron microscopic levels. Both peroxidase and pre-embedding immunogold methods were utilized. Immunoreactivity for both D1 and D2 receptors was most abundant in the neostriatum where it was mainly contained within spiny dendrites and in perikarya. Although some of the immunoreactive perikarya had characteristics of interneurons, most were identified as medium-sized spiny neurons. Immunoreactivity for D1 receptor but not D2 receptor was associated with the axons of the striatonigral pathway and axons and terminals in the substantia nigra pars reticulata and the entopeduncular nucleus. In contrast, D2 immunoreactivity but not D1 immunoreactivity was present in the dopaminergic neurons in the substantia nigra pars compacta and ventral pars reticulata. In the globus pallidus, little immunoreactivity for either D1 or D2 receptor was detected. At the subcellular level, D1 and D2 receptor immunoreactivity was found to be mainly associated with the internal surface of cell membranes. In dendrites and spines immunoreactivity was seen in contact with the membranes postsynaptic to terminals forming symmetrical synapses and less commonly, asymmetrical synapses. The morphological features and membrane specializations of the terminals forming symmetrical synapses are similar to those of dopaminergic terminals previously identified by immunocytochemistry for tyrosine hydroxylase. In addition to immunoreactivity associated with synapses, a high proportion of the immunoreactivity was also on membranes at non-synaptic sites. It is concluded that dopamine receptor immunoreactivity is mainly associated with spiny output neurons of the neostriatum and that there is a selective association of D1 receptors with the so-called direct pathway of information flow through the basal ganglia, i.e. the striatoentopeduncular and striatonigral pathways. Although there is an association of receptor immunoreactivity with afferent synaptic inputs a high proportion is located at extrasynaptic sites.

Animals↗
PubMed1995

Cholinergic, GABAergic, and glutamate-enriched inputs from the mesopontine tegmentum to the subthalamic nucleus in the rat.

In order to clarify the origin and to examine the neurochemistry and synaptology of the projection from the mesopontine tegmentum (MTg) to the subthalamic nucleus (STN), rats received discrete deposits of anterograde tracers in different regions of the MTg. Anterogradely labeled fibers were examined in the light and electron microscopes. The distribution of GABA or glutamate immunoreactivity was examined by post-embedding immunocytochemistry. The anterograde tracing demonstrated that the projection to the STN arises from at least three divisions of the MTg: the area defined by the cholinergic neurons of the pedunculopontine region (PPN-Ch 5), the more medial and largely noncholinergic midbrain extrapyramidal area (MEA) and to a lesser extent the laterodorsal tegmental nucleus (LDTg). Post-embedding immunocytochemistry revealed that there are GABA-immunopositive and immunonegative components to this projection and at least a proportion of the GABA-immunonegative component is enriched in glutamate immunoreactivity. The similarity of the morphology, trajectory and synaptology of the anterogradely labeled fibers and the choline acetyltransferase (ChAT)-immunopositive fibers supports the proposal that at least part of the projection is cholinergic. The terminals anterogradely labeled from the MTg and the ChAT-immunoreactive terminals form asymmetrical synapses with the dendrites and spines of subthalamic neurons. Both anterogradely labeled and ChAT-positive terminals make convergent synaptic contacts with GABA-immunoreactive terminals that form symmetrical synaptic contacts and are probably derived from the globus pallidus. Taken together these findings imply that the MTg sends cholinergic, GABAergic and glutamatergic projections to the STN where at least one of the functional roles is to modulate the indirect pathway of information flow through the basal ganglia that is carried via the pallidosubthalamic projection.

Afferent Pathways↗
PubMed1995

Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents.

The precise localization of D1 and D2 dopamine receptors within striatal neurons and circuits is crucial information for further understanding dopamine pharmacology. We have used subtype specific polyclonal and monoclonal antibodies against D1 and D2 dopamine receptors to determine their cellular and subcellular distributions, their colocalization, and their differential connectivity with motor cortical afferents labeled either by lesion-induced degeneration or by anterograde transport of biotinylated dextrans. D1 and D2 are primarily expressed in medium-sized neurons and spiny dendrites. Axon terminals containing D1 were rare whereas D2-immunoreactive axon terminals forming symmetrical synapses with dendrites and spines were common. In 2 microns sections, D1 was localized to 53% of neurons, and D2 to 48% of neurons, while mixing D1 and D2 antibodies labeled 78%. By electron microscopy, D1 was localized to 43% of dendrites and 38% of spines while D2 was localized to 38% of dendrites and 48% of spines. Combining D1 and D2 antibodies resulted in the labeling of 88.5% of dendrites and 92.6% of spines. Using different chromogens for D1 and D2, colocalization was not observed. Ipsilateral motor corticostriatal afferents were primarily axospinous and significantly more synapsed with D1 than D2-positive spines (65% vs 47%). Contralateral motor corticostriatal afferents were frequently axodendritic and no difference in their frequency of synapses with D1 and D2 dendrites and spines was observed. These findings demonstrate differential patterns of expression of D1 and D2 receptors in striatal neurons and axon terminals and their differential involvement in motor corticostriatal circuits.

Animals↗
PubMed1994

Neurons projecting from the entopeduncular nucleus to the thalamus receive convergent synaptic inputs from the subthalamic nucleus and the neostriatum in the rat.

The two major afferents of the entopeduncular nucleus are the subthalamic nucleus and the neostriatum, which have opposing physiological effects on entopeduncular neurons. Experiments were performed to test the hypothesis that individual entopeduncular neurons that project to the thalamus receive convergent synaptic input from both the subthalamic nucleus and the neostriatum in the rat. This was achieved using double anterograde tracing combined with retrograde tracing. In the electron microscope anterogradely labelled subthalamic (Subthalamic Type 1) and neostriatal terminals were observed to form asymmetrical and symmetrical synaptic contacts respectively, with all parts of entopeduncular neurons. Labelled subthalamic and neostriatal terminals were observed in convergent synaptic contact with entopeduncular neurons, some of which were retrogradely labelled from the thalamus. A second rarer type of terminal was labelled (Subthalamic Type 2) which formed symmetrical synaptic contacts with the proximal regions of unlabelled and retrogradely labelled entopeduncular neurons. These terminals are believed to be derived from the globus pallidus. It is concluded that the topographical and synaptic organization of the so-called direct (neostriatum to entopeduncular nucleus) and indirect pathways (involving the subthalamus and the globus pallidus) is capable of mediating the inhibition and excitation of output neurons in the entopeduncular nucleus that occur following neostriatal stimulation.

Animals↗
PubMed1994

Localisation of parvalbumin-immunoreactive structures in primate caudate-putamen.

To investigate the morphology, distribution, and connections of parvalbumin-containing neurones in the caudate-putamen of primates, perfuse-fixed sections were stained to reveal parvalbumin immunoreactivity. In agreement with previous observations, the caudate-putamen was rich in parvalbumin-positive neurones and neuropil. The neuropil staining was uneven such that the dense background staining was interspersed with zones of relatively weak staining. The distribution corresponded to the striosome/matrix system as defined by substance P or met-enkephalin immunostaining in adjacent sections. Because parvalbumin-positive neurones are present in regions known to project to the caudate-putamen and the majority of parvalbumin-positive terminals in the matrix formed asymmetric synapses, it is concluded that the uneven staining is probably due to afferents of the neostriatum. The morphology of the parvalbumin-immunoreactive neurones varied between the striosomes and matrix; those in the matrix were smaller and possessed dendritic arborisations that were relatively uniform, whereas those in the striosomes were generally more extensively stained and possessed a greater variation in their dendritic branching patterns. The dendrites frequently crossed the boundary between the striosomes and matrix. A population of giant parvalbumin-immunoreactive neurones was also observed in the putamen. Electron microscopic analysis revealed that, in addition to terminals forming asymmetric synapses, a smaller population formed symmetric synaptic specialisations and are presumed to be derived from the local parvalbumin-immunoreactive neurones. Terminals of the latter group formed synapses with medium-sized spiny neurones. Because parvalbumin-positive neurones receive input from the cortex, they may transmit cortical information to spiny neurones.

Animals↗
PubMed1994

The effect of kainic acid on the release of GABA in rat neostriatum and substantia nigra.

In order to test the hypotheses that stimulation of non-N-methyl-D-aspartate (NMDA) receptors in the neostriatum causes the release of gamma-aminobutyric acid (GABA) from nigrostriatal neurones, dual microdialysis was carried out in the neostriatum and substantia nigra of freely moving rats. Application of kainic acid to the neostriatum caused a dose-dependent release of GABA both locally and, at the same time, from the ipsilateral substantia nigra. These effects were blocked by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Direct application of kainic acid to the substantia nigra caused a DNQX-sensitive local release of GABA. It is concluded that excitatory amino acid receptor stimulation of the neostriatum releases GABA from striatonigral neurones and that stimulation of the substantia nigra causes the release from striatonigral terminals and/or the collaterals of nigrofugal neurones.

Animals↗
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

Convergent synaptic input from the neostriatum and the subthalamus onto identified nigrothalamic neurons in the rat.

The two major afferents of the substantia nigra pars reticulata are the subthalamic nucleus and the striatum. Stimulation of these afferents has opposing physiological effects on the output neurons of the substantia nigra pars reticulata. In order to better understand the role of these afferents in the flow of information through the basal ganglia and to better understand the ways in which they might interact, experiments have been performed to test the possibility that single-output neurons of the substantia nigra pars reticulata receive convergent synaptic input from the subthalamic nucleus and the neostriatum. To address this, rats received iontophoretic deposits of the anterograde tracer Phaseolus vulgaris leucoagglutinin in the subthalamic nucleus, injections of the anterograde tracer biocytin in the neostriatum and injections of the retrograde tracer horseradish peroxidase conjugated to wheat-germ agglutinin in the ventral medial nucleus of the thalamus. Following appropriate survival times the animals were perfusion-fixed and sections of the substantia nigra were processed to reveal the transported tracers and prepared for electron microscopy. Light microscopic examination revealed that the substantia nigra contained rich plexuses of anterogradely labelled subthalamic and striatal terminals, as well as many retrogradely labelled nigrothalamic neurons. The anterogradely labelled terminals were often seen apposed to the retrogradely labelled neurons. In the electron microscope the subthalamic terminals were seen to form asymmetrical synaptic contacts (subthalamic type 1) with the identified nigrothalamic neurons as well as unlabelled perikarya and both proximal and distal dendrites. In confirmation of previous findings, the striatal terminals made symmetrical synaptic contact with the nigrothalamic neurons as well as unlabelled neurons. In areas of overlap between the two classes of terminals, identified nigrothalamic neurons and unlabelled nigral neurons were found to receive convergent synaptic input from the subthalamic nucleus and the neostriatum. In addition to the anterogradely labelled subthalamic terminals that formed asymmetrical synaptic specializations, a second, much rarer class was also observed (subthalamic type 2). These terminals were much larger and formed symmetrical synapses; several lines of evidence suggest that they originated not in the subthalamic nucleus but in the globus pallidus. These terminals were found to make synaptic contacts with identified nigrothalamic neurons and non-labelled neurons and to form convergent synaptic contacts with subthalamic type 1 terminals and striatal terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗