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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey. 150 1

Previous studies have demonstrated that the calcium-binding protein parvalbumin, is located within a population of GABAergic interneurons in the neostriatum of the rat. Anatomical studies have revealed that these cells receive asymmetrical synaptic input from terminals that are similar to identified cortical terminals and that they innervate neurons with the ultrastructural features of medium spiny cells. Furthermore, electrophysiological studies suggest that some GABAergic interneurons in the neostriatum receive direct excitatory input from the cortex and inhibit medium spiny cells following cortical stimulation. The main objectives of the present study were (i) to determine whether parvalbumin-immunoreactive neurons in the rat receive direct synaptic input from the cortex, (ii) to determine whether parvalbumin-immunopositive axon terminals innervate identified striatal projection neurons and (iii) to chemically characterize this anatomical circuit at the fine structural level. Rats received stereotaxic injections of biocytin in the frontal cortex or injections of neurobiotin in the substantia nigra. Following an appropriate survival time, the animals were perfused and the brains were sectioned and treated to reveal the transported tracers. Sections containing the neostriatum were treated for simultaneous localization of the transported tracer and parvalbumin immunoreactivity. Tracer deposits in the cortex gave rise to massive terminal and fibre labelling in the neostriatum. Parvalbumin-immunoreactive elements located within fields of anterogradely labelled terminals were examined in the electron microscope and corticostriatal terminals were found to form asymmetrical synaptic specializations with all parts of parvalbumin-immunoreactive neurons that were examined. Tracer deposits in the substantia nigra produced retrograde labelling of a subpopulation of striatonigral neurons. Areas of the neostriatum and nucleus accumbens containing retrogradely labelled neurons and parvalbumin-immunoreactive structures were selected for electron microscopy. Parvalbumin-immunopositive axon terminals formed symmetrical synaptic specializations with the perikarya of retrogradely labelled medium spiny projection neurons. Postembedding immunocytochemistry for GABA revealed that parvalbumin-immunoreactive boutons in synaptic contact with medium spiny neurons were GABA-positive. These data demonstrate directly a neural circuit whereby cortical information may be passed to medium spiny cells, via GABAergic interneurons, in the form of inhibition and provide an anatomical substrate for the feed-forward inhibition that has been detected in spiny neurons in electrophysiological experiments.
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PMID:Synaptic input and output of parvalbumin-immunoreactive neurons in the neostriatum of the rat. 787 Mar 1

The complete axon arborization of a single CA3 pyramidal cell has been reconstructed from 32 (60 microns thick) sections from the rat hippocampus following in vivo intracellular injection of neurobiotin. The same sections were double-immunostained for parvalbumin--a calcium-binding protein selectively present in two types of GABAergic interneurons, the basket and chandelier cells--in order to map boutons of the pyramidal cell in contact with dendrites and somata of these specific subsets of interneurons visualized in a Golgi-like manner. The axon of the pyramidal cell formed 15,295 boutons, 63.8% of which were in stratum oriens, 15.4% in stratum pyramidale and 20.8% in stratum radiatum. Only 2.1% of the axon terminals contacted parvalbumin-positive neurons. Most of these were single contacts (84.7%), but double or triple contacts (15.3%) were also found. The majority of the boutons terminated on dendrites (84.1%) of parvalbumin-positive cells, less frequently on cell bodies (15.9%). In order to estimate the proportion of contacts representing synapses, 16 light microscopically identified contacts between boutons of the filled pyramidal cell axon and the parvalbumin-positive targets were examined by correlated electron microscopy. Thirteen of them were found to be asymmetrical synapses, and in the remaining three cases synapses between the labelled profiles could not be confirmed. We conclude that the physiologically effective excitatory connections between single pyramidal cells and postsynaptic inhibitory neurons are mediated by a small number of contacts, mostly by a single synapse. This results in a high degree of convergence and divergence in hippocampal networks.
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PMID:Complete axon arborization of a single CA3 pyramidal cell in the rat hippocampus, and its relationship with postsynaptic parvalbumin-containing interneurons. 812 22

NMDA receptors are composed of multiple receptor subunit proteins, of which NMDAR1 appears to be a critical component for normal receptor function (Nakanishi, 1992). In this study, quantitative immunocytochemical methods were used at the light and electron microscopic levels to localize NMDAR1 subunits in the primary motor (M1) and somatic sensory (S1) cortex of monkeys, and in the primary visual cortices (V1) of monkey and human. Three principal features of NMDAR1 subunit organization were examined in detail in the monkey cortex: (1) the laminar and cellular distribution patterns, relying in part on double-labeling paradigms with the calcium-binding proteins parvalbumin (PV) and calretinin (CR) as markers for discrete subpopulations of GABAergic interneurons; (2) the codistribution of NMDAR1 subunits with non-NMDA ionotropic receptor subunits; (3) a quantitative assessment of the percentages of asymmetrical synapses in layers II/III, IV, and V/VI that were NMDAR1 immunoreactive. In monkey M1, S1, and V1, NMDAR 1 immunoreactivity was present in all layers, localized primarily to large numbers of pyramidal cell somata and proximal apical dendrites, to presumptive spiny stellate cells in layer IV of V1, and to the vast majority (approximately 80-90%) of PV-immunoreactive cells. By contrast, NMDAR1 immunoreactivity was present in only a very small percentage of the CR-immunoreactive cells (approximately 6-9%). Colocalization with non-NMDA receptor subunits showed that all cells (100%) that contained GluR2/3 subunits were also NMDAR1 immunoreactive. In addition, the complete codistribution of GluR5/6/7 subunits with GluR2/3 subunits suggests, indirectly, that all GluR5/6/7-immunoreactive cells are also NMDAR1 immunoreactive. The laminar and cellular distribution patterns of immunostaining in human V1 were very similar to those in monkey V1. Electron microscopy of monkey sections confirmed an extensive dendritic and synaptic localization of NMDAR1 subunits. Labeling of synapses was present on asymmetrical postsynaptic densities associated with both dendritic shafts and spines. In supragranular layers of V1, a greater percentage of asymmetrical synapses were NMDAR1 immunopositive (44%) in comparison to layer IVC beta (34%) or deep layers (19%). In contrast, in area 3b of S1, the percentage of labeled synapses was greatest in layer IV (45%) in comparison to superficial (26%) and deep (37%) layers, while in M1, the percentages of labeled synapses were similar between superficial (46%) and deep (40%) layers. Taken together, these data indicate that NMDAR1-immunoreactive cells in neocortex represent a morphologically, functionally, and neurochemically heterogeneous population.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Distribution and synaptic localization of immunocytochemically identified NMDA receptor subunit proteins in sensory-motor and visual cortices of monkey and human. 820 75

The distribution of the calcium binding protein, calretinin (CR) has been investigated immunohistochemically in the cerebral cortex of albino rats by light- and electron microscopy. At the light microscopical level the pattern of CR-immunoreactivity (ir) appeared very similar in all regions of the rat cerebral cortex. CR-immunoreactive cells were found sparsely in layer I to layer VI, and frequently also in the white matter of the corpus callosum. All CR-ir neurons revealed morphological characteristics of local interneurons. The calretinin positive interneurons could be grouped according to their laminar occurrence, dendritic arborization and the soma size into 5 cell type classes. Quantitative measurements were performed only in the visual cortex. CR-ir neurons were more frequent in the superficial layers II and III. In all other layers, CR-ir cells are sparsely distributed with no preferential laminar localization. At the electron microscopical level, CR-ir axonal boutons formed frequently symmetrical axo-dendritic contacts. In all animals we observed CR-ir axons forming also synaptses of asymmetrical type. In summary calretinin labelled an interneuronal subpopulation of the rat cerebral cortex, which seemed not to overlap in its distribution and labelled structures to those, containing the related calcium binding proteins parvalbumin and calbindin D-28k.
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PMID:The calcium-binding protein calretinin is localized in a subset of interneurons in the rat cerebral cortex: a light and electron immunohistochemical study. 837 59

Previous observations have shown that the striatum contains a population of neurones that display immunoreactivity for calretinin. In order to morphologically characterize these neurones, sections of the rat striatum were immunostained to reveal calretinin and examined at both light and electron microscopic levels. The striatum contained a small population of calretinin-immunoreactive neurones, which were of medium-size (9-17 microns) and possessed few aspiny, infrequently branching dendrites which tapered to become very thin processes in their most distal portions. Although the calretinin-immunoreactive neurones were homogeneously distributed in the frontal plane, there was a marked rostrocaudal gradient with a much greater density of cells in the rostral than in the caudal parts of the striatum. At the ultrastructural level, calretinin-immunoreactive neurones were seen to possess an indented nucleus and to receive synaptic input from at least three types of boutons. In addition to the calretinin-immunoreactive neurones, the striatum also contained axons and terminal boutons that displayed immunoreactivity for calretinin. At least two types of immunoreactive terminals were identified, those forming symmetrical synaptic specialisations and those forming asymmetrical synaptic specialisations. Approximately 50% formed asymmetrical contacts with spines and 30% formed symmetrical synaptic contact with dendritic shafts. In an attempt to further chemically characterize the calretinin-containing neurones, double pre-embedding immunocytochemistry for calretinin and parvalbumin or choline acetyltransferase was carried out and calretinin immunocytochemistry was combined with histochemistry for NADPH-diaphorase. Analysis of these double-stained sections revealed that the population of calretinin-immunoreactive neurones was distinct from the populations of neurones containing parvalbumin, choline acetyltransferase or NADPH-diaphorase. It is concluded that: (1) on the basis of distribution, morphology, chemistry, ultrastructure and afferent synaptic input, the calretinin-immunoreactive neurones are distinct from the major classes of neurones that have been previously recognised in the striatum; (2) calretinin-immunoreactive terminals are heterogeneous and are probably derived from local calretinin-containing neurones and possibly other sources.
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PMID:Characterization of calretinin-immunoreactive structures in the striatum of the rat. 850 97

The rat nucleus accumbens contains medium-sized, spiny projection neurons and intrinsic, local circuit neurons, or interneurons. Sub-classes of interneurons, revealed by calretinin (CR) or parvalbumin (PV) immunoreactivity or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, were compared in the nucleus accumbens core, shell and rostral pole. CR, PV and NADPH-diaphorase-containing neurons are shown to form three non-co-localising populations in these three areas. No significant differences in neuronal population densities were found between the subterritories. NADPH-diaphorase-containing neurons could be further separated morphologically into three sub-groups, but CR- and PV-immunoreactive neurons form homogeneous populations. Ultrastructurally, NADPH-diaphorase-, CR- and PV-containing neurons in the nucleus accumbens all possess nuclear indentations. These are deeper and fewer in neurons immunoreactive for PV than in CR- and NADPH-diaphorase-containing neurons. CR-immunoreactive boutons form asymmetrical and symmetrical synaptic specialisations on spines, dendrites and somata, while PV-immunoreactive boutons make only symmetrical synaptic specialisations. Both CR- and PV-immunoreactive boutons form symmetrical synaptic specialisations with medium-sized spiny neurons and contact other CR- and PV-immunoreactive somata, respectively. A novel non-carcinogenic substrate for the peroxidase reaction (Vector Slate Grey, SG) was found to be characteristically electron-dense and may be distinguishable from the diaminobenzidine reaction product. We conclude that the three markers used in this study are localised in distinct populations of nucleus accumbens interneurons. Our studies of their synaptic connections contribute to an increased understanding of the intrinsic circuitry of this area.
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PMID:A light and electron microscopic study of NADPH-diaphorase-, calretinin- and parvalbumin-containing neurons in the rat nucleus accumbens. 870 62

Neurons containing a calcium-binding protein parvalbumin in the external plexiform layer of the rat olfactory bulb were identified light microscopically with the pre-embedding immunocytochemistry and were subsequently analysed with the electron microscopic serial-sectioning and three-dimensional reconstructions. In the present study we chose several different types of parvalbumin-immunoreactive neurons identified light microscopically as Van Gehuchten cell type, superficial short-axon cell type and multipolar cell type. Parvalbumin-immunoreactive somata were similar to one another in their ultrastructural characteristics, showing nuclear indentations, moderately developed Golgi apparatus and abundant mitochondria; these structural features appeared to resemble those of the short axon cells around the glomeruli and in the granule cell layer reported in previous electron microscopic studies. All neurons analysed in the present study made symmetrical synapses on to dendrites and somata of presumed mitral/tufted cells and received asymmetrical synapses from them, and occasionally formed reciprocal synapses with them. On the parvalbumin-immunoreactive processes, the asymmetrical synapses nearly equalled the symmetrical ones in number and about 30-50% of them were identified as reciprocal pairs. In contrast, no presynaptic sites were observed on parvalbumin-immunoreactive somata, and thick portions (more than approximately 2 microns in diameter) of the proximal dendrites, where they were occasionally postsynaptic in some asymmetrical and symmetrical synapses from parvalbumin-immunonegative profiles. Characteristically, parvalbumin-immunoreactive process frequently make direct contacts with one another; processes regarded light microscopically as arising from a soma or a dendrite or parvalbumin-immunoreactive neurons were sometimes revealed to be separate but directly contacting processes with electron microscopic examinations. Although puncta adherentia were occasionally observed between these contact sites, so far neither gap junctions nor chemical synapses were observed. Until now, it has been believed that in the external plexiform layer only granule cells form reciprocal synapses with mitral/tufted cells. However, the present study clearly demonstrates that interneurons different from granule cells, namely GABAergic neurons containing a calcium-binding protein parvalbumin, also make reciprocal synapses with mitral/tufted cells in the external plexiform layer. Therefore, neuronal processes making reciprocal synapses with mitral/tufted cells in the external plexiform layer cannot be determined a priori as granule cell processes.
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PMID:Electron microscopic serial-sectioning/reconstruction study of parvalbumin-containing neurons in the external plexiform layer of the rat olfactory bulb. 873 15

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.
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PMID:Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat. 898 3

The cellular and synaptic localization of immunoreactivity for the N-methyl-D-aspartate (NMDA) receptor subunit, NMDAR1, was investigated in inferotemporal and prefrontal association neocortices of monkeys and humans. In all monkey association areas examined, the laminar distribution patterns of NMDAR1 immunoreactivity were similar, and characterized by predominant pyramidal-like neuronal labeling in layers II, III, V and VI and a dense neuropil labeling consisting of intensely stained puncta and fine-caliber processes present throughout layers I-III, and V-VI. Layer IV, in contrast, contained only very lightly immunostained neurons which mostly lacked extensive dendritic staining. The laminar distribution of NMDAR1 immunolabeling in human association cortex was similar to that observed in monkeys. Electron microscopy of monkey areas 46 and TE1 confirmed that intensely immunoreactive asymmetrical postsynaptic densities were present throughout all cell-dense layers of prefrontal and inferotemporal association cortex. Quantitative analyses of the laminar proportions of immunoreactive synapses demonstrated that in both areas examined, the percentages of immunolabeled synapses were mostly similar across superficial layers, layer IV and infragranular layers. Finally, quantitative double-labeling immunofluorescence for non-NMDA receptor subunits or calcium-binding proteins demonstrated that virtually all GluR2/3 or GluR5/6/7-immunoreactive neurons were also labeled for NMDAR1, while regionally-specific subsets of parvalbumin-, calbindin- and calretinin-immunoreactive neurons were co-labeled. These data indicate that in primate association cortex, NMDA receptors are heterogeneously distributed to subsets of functionally distinct types of neurons and subsets of excitatory synapses, suggesting a critical and highly specific role in mediating the activity of excitatory connectivity which converges on cortical association areas.
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PMID:Quantitative localization of NMDAR1 receptor subunit immunoreactivity in inferotemporal and prefrontal association cortices of monkey and human. 913 25


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