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J P Bolam

Publications and source records attributed to J P Bolam.

At least 19 recordsLinked to original sources
PubMed2000

Localization of dopamine D1 and D2 receptors in the rat neostriatum: synaptic interaction with glutamate- and GABA-containing axonal terminals.

In order to determine the synaptic interactions between the glutamate- and GABA-containing axonal terminals and the two subpopulations of medium spiny neurons in the rat neostriatum, double immunocytochemistry was performed. Sections of perfuse-fixed rats were used. Immunoreactivity for dopamine D1 and D2 receptors was used as a marker for the two subpopulations of spiny neurons that give rise to the direct and indirect pathways, respectively. Receptor immunoreactivity was first revealed by preembedding immunostaining. Postembedding colloidal gold labeling was then performed to reveal immunoreactivity for glutamate or GABA. The results were analyzed at the electron microscopic level. Both the D1-immunoreactive, presumed striatonigral/entopeduncular neurons, and the D2-immunoreactive, presumed striatopallidal neurons, were found to receive qualitatively similar synaptic inputs from glutamate-immunoreactive terminals and GABA-immunoreactive terminals. The present results indicate that the different classes of spiny neurons are thus likely to be under a similar regime of excitatory and inhibitory control.

Animals↗
PubMed2000

Cellular and sub-cellular localisation of GABA(B1) and GABA(B2) receptor proteins in the rat cerebellum.

Following the recent discovery that GABA(B) receptors expressed in cell lines are only functional when both GABA(B1) and GABA(B2) are expressed, the present study reports on the development of polyclonal antisera specific for carboxyl-terminal portions of the two related GABA(B) receptor components respectively. Western blotting indicated the specificity of affinity-purified antibodies for native or recombinant expressed GABA(BR1) and GABA(BR2), with no cross-reactivity, both antisera detecting the heterodimer in rat cerebellar membranes. Immunohistochemistry revealed a distinct distribution of both receptor proteins in rat cerebellum. GABA(B1) immunoreactivity was primarily located in the granule cell layer and Purkinje cells, with discrete immuno-positive cell bodies being present in the molecular layer. GABA(B2) staining revealed intense immunoreactivity in the molecular layer, with weaker staining in the granule cell layer. Purkinje cell bodies were less intensely immuno-positive for GABA(B2). Co-localisation of both receptor proteins was observed using double immunofluorescence techniques, consistent with the notion that both proteins are required for the formation of functional GABA(B) receptors in vivo. Immunofluorescence also indicated that GABA(B) receptors did not co-localise with glial fibrillary acid protein, confirming a neuronal localisation for GABA(B) receptors. Electron microscopic analysis of the molecular layer revealed that the distribution of immunolabelling for both GABA(B1) and GABA(B2) was mainly located on the membrane of Purkinje cell dendrites and spines and in parallel fibre terminals.

Animals↗
PubMed2000

Distribution of the neurotensin receptor NTS1 in the rat CNS studied using an amino-terminal directed antibody.

The distribution of neurotensin receptor 1 immunoreactivity in the rat brain was studied using an antibody against the amino-terminal of the receptor expressed as a fusion protein with glutathione-S transferase. Affinity purified antibodies detected the fusion protein and the complete neurotensin receptor sequence expressed in Escherichia coli. The immunostaining was abolished by preabsorption with the amino-terminal fusion protein. Immunoreactive neurotensin receptor 1 immunoreactivity was detected on cell bodies and their processes in a number of CNS regions. In agreement with previous binding studies neurotensin receptor 1 immunoreactivity was particularly localised in cell bodies in the basal forebrain, nucleus basalis and substantia nigra. At the electron microscope level immunoreactivity was found both in axonal bouton and dendrites and spines in the basal forebrain indicating that neurotensin may act both pre- and post-synaptically. There were several regions such as the substantia gelatinosa, ventral caudate-putamen and the lateral reticular nucleus where the neurotensin receptor 1 positive cells had not previously been reported, indicating that distribution of this receptor is widespread.

Animals↗
PubMed2000

Relationship of activity in the subthalamic nucleus-globus pallidus network to cortical electroencephalogram.

One of the functions of the excitatory subthalamic nucleus (STN) is to relay cortical activity to other basal ganglia structures. The response of the STN to cortical input is shaped by inhibition from the reciprocally connected globus pallidus (GP). To examine the activity in the STN-GP network in relation to cortical activity, we recorded single and multiple unit activity in STN and/or GP together with cortical electroencephalogram in anesthetized rats during various states of cortical activation. During cortical slow-wave activity (SWA), STN and GP neurons fired bursts of action potentials at frequencies that were similar to those of coincident slow ( approximately 1 Hz) and spindle (7-14 Hz) cortical oscillations. Spontaneous or sensory-driven global activation was associated with a reduction of SWA and a shift in STN-GP activity from burst- to tonic- or irregular-firing. Rhythmic activity in STN and GP neurons was lost when the cortex was inactivated by spreading depression and did not resume until SWA had recovered. Although rhythmic STN-GP activity was correlated with SWA, the phase relationships of activities of neurons within the STN and GP and between the nuclei were variable. Even when neurons displayed synchronous bursting activity, correlations on the millisecond time scale, which might indicate shared synaptic input, were not observed. These data indicate that (1) STN and GP activity is intimately related to cortical activity and hence the sleep-wake cycle; (2) rhythmic oscillatory activity in the STN-GP network in disease states may be driven by the cortex; and (3) activity of the STN-GP network is regulated in space in a complex manner.

Action Potentials↗
PubMed2000

Synaptic localization of GABA(A) receptor subunits in the striatum of the rat.

The inhibitory amino acid gamma-aminobutyric acid (GABA) is widely distributed in the basal ganglia. It plays a critical role in the functioning of the striatum as it is the transmitter of projection neurons and sub-populations of interneurons, as well as afferents from the globus pallidus. Some of the factors controlling GABA transmission are the type(s) of GABA receptor expressed at the site of transmission, their subunit composition, and their location in relation to GABA release sites. To address these issues, we examined the sub-cellular localization of subunits of the GABA(A) receptor in the striatum of the rat. Sections of freeze-substituted, Lowicryl-embedded striatum were immunolabelled by the post-embedding immunogold technique with antibodies specific for subunits of the GABA(A) receptor. Immunolabelling for alpha1, beta2/3, and gamma2 GABA(A) receptor subunits was primarily located at symmetrical synapses on perikarya, dendrites, and spines. Quantitative analysis of the distribution of immunolabelling for the beta2/3 subunits revealed that the majority of membrane associated immunogold particles were at synapses and that, on average for the whole population, they were evenly distributed across the synapse. Double labelling for the beta2/3 subunits and for GABA itself revealed that receptor-positive synapses were formed by at least two populations of terminals. One population (59.3%) of terminals forming receptor-positive synapses was positive for GABA, whereas the other (40.7%) had low or undetectable levels of GABA. Furthermore, the post-synaptic neurons were characterised on neurochemical and morphological grounds as both medium spiny neurons and GABA interneurons. Triple immunolabelling revealed the co-localization of alpha1, beta2/3, and gamma2 subunits at some symmetrical axodendritic synapse. It is concluded that fast GABA(A)-mediated transmission occurs primarily at symmetrical synapses within the striatum, that the populations of boutons giving rise to receptor-positive synapses are heterogeneous, and that previously reported co-existence of different subunits of the GABA(A) receptor at the cellular level also occurs at the level of individual synapses.

Animals↗
PubMed2000

Synaptic localization of ionotropic glutamate receptors in the rat substantia nigra.

Glutamatergic neurotransmission in the substantia nigra pars compacta and pars reticulata is mediated through N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxaline propionic acid/kainate (AMPA) type receptors as well as other glutamate receptors and is critical for basal ganglia functioning. A major glutamatergic input to the substantia nigra originates in the subthalamic nucleus, and the long-lasting stimulation of the dopaminergic cells of the substantia nigra pars compacta by the subthalamic neurons has been implicated in the pathophysiology of Parkinson's disease. The objectives of the present study were to determine the subcellular and subsynaptic localization of subunits of the N-methyl-D-aspartate and AMPA receptors in the substantia nigra, and also to determine whether co-localization of N-methyl-D-aspartate and AMPA receptor subunits occur at individual synapses. To achieve this, pre-embedding and post-embedding immunocytochemistry was applied to sections of substantia nigra using antibodies that recognize the NR1 and NR2A/B subunits of the N-methyl-D-aspartate receptor, and GluR2/3 subunits of the AMPA receptor. In both regions of the substantia nigra, immunolabelling for each of the subunits was observed in numerous perikarya and proximal dendrites. At the subcellular level, silver-intensified immunogold particles localizing N-methyl-D-aspartate and AMPA receptor subunits were most commonly present within dendrites where they were associated with a variety of intracellular organelles and with the internal surface of the plasma membrane. Post-embedding immunogold labelling revealed immunoparticles labelling for NR1, NR2A/B and GluR2/3 to be enriched at asymmetric synaptic specializations, although a large proportion of asymmetric synapses were immunonegative. Double immunolabelling revealed, in addition to single-labelled synapses, the co-localization of subunits of the N-methyl-D-aspartate receptor and subunits of the AMPA receptor at individual asymmetric synapses. Similarly, double immunolabelling also revealed the co-localization of the NRl and NR2A/B subunits of the N-methyl-D-aspartate receptor at individual asymmetric synapses. Labelling for NR1 and GluR2/3 was, on average, relatively evenly distributed across the width of the synapse with a gradual reduction towards the periphery when analysed in single sections. In summary, the present results demonstrate that AMPA and N-methyl-D-aspartate receptors are selectively localized at a subpopulation of asymmetric synapses in the substantia nigra pars compacta and reticulata and that the two receptor types, at least partially co-localize at individual synapses. It is concluded that glutamatergic transmission in the substantia nigra pars compacta and pars reticulata occurs primarily at asymmetric synapses and, at least in part, is mediated by both N-methyl-D-aspartate and AMPA receptors.

Animals↗
PubMed2000

Synaptic organisation of the basal ganglia.

The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context-dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is 'processed' within the striatum and passed via the so-called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical 'premotor' regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed-forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic integration of functionally diverse information derived from the cortex. It is concluded that the essential concept of the direct and indirect pathways of information flow through the basal ganglia remains intact but that the role of the indirect pathway is more complex than previously suggested and that neurons of the globus pallidus are in a position to control the activity of virtually the whole of the basal ganglia.

Animals↗
PubMed2000

Equilibrium potential of GABA(A) current and implications for rebound burst firing in rat subthalamic neurons in vitro.

Reciprocally connected glutamatergic subthalamic and GABAergic globus pallidus neurons have recently been proposed to act as a generator of low-frequency oscillatory activity in Parkinson's disease. To determine whether GABA(A) receptor-mediated synaptic potentials could theoretically generate rebound burst firing in subthalamic neurons, a feature that is central to the proposed oscillatory mechanism, we determined the equilibrium potential of GABA(A) current (E(GABA(A))) and the degree of hyperpolarization required for rebound firing using perforated-patch recording. In the majority of neurons that fired rebounds, E(GABA(A)) was equal to or more hyperpolarized than the hyperpolarization required for rebound burst firing. These data suggest that synchronous activity of pallidal inputs could underlie rhythmic bursting activity of subthalamic neurons in Parkinson's disease.

Animals↗
PubMed1998

Selective innervation of neostriatal interneurons by a subclass of neuron in the globus pallidus of the rat.

A subpopulation of neurons in the globus pallidus projects to the neostriatum, which is the major recipient of afferent information to the basal ganglia. Given the moderate nature of this projection, we hypothesized that the pallidostriatal projection might exert indirect but powerful control over principal neuron activity by targeting interneurons, which comprise only a small percentage of neostriatal neurons. This was tested by the juxtacellular labeling and recording of pallidal neurons in combination with immunolabeling of postsynaptic neurons. In addition to innervating the subthalamic nucleus and output nuclei, 6 of 23 labeled pallidal neurons projected to the neostriatum. Both the firing characteristics and the extent of the axonal arborization in the neostriatum were variable. However, light and electron microscopic analysis of five pallidostriatal neurons revealed that each neuron selectively innervated neostriatal interneurons. A large proportion of the boutons of an individual axon (19-66%) made contact with parvalbumin-immunoreactive interneurons. An individual parvalbumin-immunoreactive neuron (n = 27) was apposed on average by 6.7 boutons (SD = 6.1) from a single pallidal axon (n = 2). Individual pallidostriatal boutons typically possessed more than one symmetrical synaptic specialization. In addition, 3-32% of boutons of axons from four of five pallidal neurons contacted nitric oxide synthase-immunoreactive neurons. Descending collaterals of pallidostriatal neurons were also found to make synaptic contact with dopaminergic and GABAergic neurons of the substantia nigra. These data imply that during periods of cortical activation, individual pallidal neurons may influence the activity of GABAergic interneurons of the neostriatum (which are involved in feed-forward inhibition and synchronization of principle neuron activity) while simultaneously patterning neuronal activity in basal ganglia downstream of the neostriatum.

Action Potentials↗
PubMed1998

Distribution of glutamate receptor subunits at neurochemically characterized synapses in the entopeduncular nucleus and subthalamic nucleus of the rat.

Glutamatergic neurotransmission in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia is critical in the expression of basal ganglia function, and increased glutamate transmission in these nuclei has been implicated in the pathology of Parkinson's disease. In order to determine the precise spatial relationship of subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors to nerve terminals enriched in glutamate or gamma-aminobutyric acid (GABA) in one of the output nuclei, the entopeduncular nucleus (EP), and the STN, postembedding immunolabelling for glutamate receptor subunits and for glutamate and GABA was carried out in the rat. Immunolabelling for the AMPA glutamate receptor subunits 1, 2/3, and 4 (GluR1, GluR2/3, and GluR4) and the NMDA receptor subunit 1 (NR1) was localized predominantly within asymmetrical synapses in both the EP and STN. Quantitative analysis revealed that, on average for the whole population, each of the receptor subunits was evenly distributed along the synaptic specialization. Multiple AMPA receptor subunits and the GluR2/3 and NMDA (NR1) subunits were co-localized within individual synapses. The combination of immunolabelling for glutamate and GABA with the receptor immunolabelling revealed that the majority of axon terminals presynaptic to the receptor-immunoreactive synapses were enriched in glutamate immunoreactivity and were GABA-immunonegative. However, at some NR1- and GluR2/3-positive synapses, the level of glutamate immunoreactivity was low in the presynaptic terminal and, in the STN, some of them were GABA-immunopositive. It is concluded that glutamatergic transmission at individual synapses of different origins in the EP and STN is mediated by a combination ofAMPA and NMDA glutamate receptors.

Animals↗
PubMed1998

Microcircuitry of the direct and indirect pathways of the basal ganglia.

Our understanding of the organization of the basal ganglia has advanced markedly over the last 10 years, mainly due to increased knowledge of their anatomical, neurochemical and physiological organization. These developments have led to a unifying model of the functional organization of the basal ganglia in both health and disease. The hypothesis is based on the so-called "direct" and "indirect" pathways of the flow of cortical information through the basal ganglia and has profoundly influenced the field of basal ganglia research, providing a framework for anatomical, physiological and clinical studies. The recent introduction of powerful techniques for the analysis of neuronal networks has led to further developments in our understanding of the basal ganglia. The objective of this commentary is to build upon the established model of the basal ganglia connectivity and review new anatomical findings that lead to the refinement of some aspects of the model. Four issues will be discussed. (1) The existence of several routes for the flow of cortical information along "indirect" pathways. (2) The synaptic convergence of information flowing through the "direct" and "indirect" pathways at the single-cell level in the basal ganglia output structures. (3) The convergence of functionally diverse information from the globus pallidus and the ventral pallidum at different levels of the basal ganglia. (4) The interconnections between the two divisions of the pallidal complex and the subthalamic nucleus and the characterization of the neuronal network underlying the indirect pathways. The findings summarized in this commentary confirm and elaborate the models of the direct and indirect pathways of information flow through the basal ganglia and provide a morphological framework for future studies.

Animals↗
PubMed1998

The release of amino acids from rat neostriatum and substantia nigra in vivo: a dual microdialysis probe analysis.

It has previously been demonstrated, in dual probe microdialysis studies, that stimulation of the neostriatum with kainic acid causes the release of GABA both locally within the neostriatum and distally in the substantia nigra, observations that are consistent with the known anatomy of the basal ganglia. The object of the present study was to further examine the characteristics of GABA release and to determine whether taurine, which has been proposed to be present in striatonigral neurons, has similar characteristics of release, and to examine the release of excitatory amino acids under the same conditions. To this end, dual probe microdialysis studies were carried out on freely-moving rats. The application of kainic acid to neostriatum enhanced the release of GABA, taurine, aspartate and glutamate locally in the neostriatum and distally in the substantia nigra. The distal release of each amino acid in the substantia nigra was sensitive to the administration of 6,7-dinitroquinoxaline-2,3-dione and tetrodotoxin to the neostriatum. Similarly the local release of GABA, aspartate and glutamate but not taurine was sensitive to the intrastriatal application of 6,7-dinitroquinoxaline-2,3-dione or tetrodotoxin. It is concluded that the release of taurine from the substantia nigra has similar characteristics to that of GABA and may be released from the terminals of striatonigral neurons following the stimulation of their cell bodies in the neostriatum. The release of taurine in the neostriatum however, is likely to be mediated mainly by different mechanisms and not related to neuronal activity. The release of excitatory amino acids is likely to involve indirect effects in the neostriatum and polysynaptic pathways in the substantia nigra.

Animals↗
PubMed1998

Subcellular and subsynaptic distribution of the NR1 subunit of the NMDA receptor in the neostriatum and globus pallidus of the rat: co-localization at synapses with the GluR2/3 subunit of the AMPA receptor.

Glutamatergic neurotransmission in the neostriatum and the globus pallidus is mediated through NMDA-type as well as other glutamate receptors and is critical in the expression of basal ganglia function. In order to characterize the cellular, subcellular and subsynaptic localization of NMDA receptors in the neostriatum and globus pallidus, multiple immunocytochemical techniques were applied using antibodies that recognize the NR1 subunit of the NMDA receptor. In order to determine the spatial relationship between NMDA receptors and AMPA receptors, double labelling was performed with the NR1 antibodies and an antibody that recognizes the GluR2 and 3 subunits of the AMPA receptor. In the neostriatum all neurons with characteristics of spiny projection neurons, some interneurons and many dendrites and spines were immunoreactive for NR1. In the globus pallidus most perikarya and many dendritic processes were immunopositive. Immunogold methods revealed that most NR1 labelling is associated with asymmetrical synapses and, like the labelling for GluR2/3, is evenly spread across the synapse. Double immunolabelling revealed that in neostriatum, over 80% of NR1-positive axospinous synapses are also positive for GluR2/3. In the globus pallidus most NR1-positive synapses are positive for GluR2/3. In both regions many synapses labelled only for GluR2/3 were also detected. These results, together with previous data, suggest that NMDA and AMPA receptor subunits are expressed by the same neurons in the neostriatum and globus pallidus and that NMDA and AMPA receptors are, at least in part, colocalized at individual asymmetrical synapses. The synaptic responses to glutamate in these regions are thus likely be mediated by both AMPA and NMDA receptors at the level of individual synapses.

Animals↗
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↗