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Masanobu Kano - One of the best experts on this subject based on the ideXlab platform.
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influence of parallel fiber purkinje cell synapse formation on postnatal development of climbing fiber purkinje cell Synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Takayuki Yoshida, Masayoshi Mishina, Masahiko Watanabe, Masanobu KanoAbstract:Abstract The climbing fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with “hypogranular” cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel fibers (PFs), and normal formation of PF–PC Synapses. Our understanding of how PF–PC synapse formation affects development of CF–PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor δ2 subunit (GluRδ2), an orphan receptor expressed selectively in PCs. Deletion of GluRδ2 results in impairment of PF–PC synapse formation, which leads to defects in development of CF–PC Synapses. In this article, we review how impaired PF–PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRδ2 knockout mice. We propose a new scheme that CF–PC Synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, “early phase” of CF synapse elimination from P7 to around P11, and “late phase” of CF synapse elimination from around P12. Normal PF–PC synapse formation is required for the “late phase” of CF synapse elimination.
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influence of parallel fiber purkinje cell synapse formation on postnatal development of climbing fiber purkinje cell Synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Masayoshi Mishina, Masahiko Watanabe, Masanobu Kano, Tomoyuki YoshidaAbstract:The climbing fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with "hypogranular" cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel fibers (PFs), and normal formation of PF-PC Synapses. Our understanding of how PF-PC synapse formation affects development of CF-PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in impairment of PF-PC synapse formation, which leads to defects in development of CF-PC Synapses. In this article, we review how impaired PF-PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout mice. We propose a new scheme that CF-PC Synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, "early phase" of CF synapse elimination from P7 to around P11, and "late phase" of CF synapse elimination from around P12. Normal PF-PC synapse formation is required for the "late phase" of CF synapse elimination.
Masahiko Watanabe - One of the best experts on this subject based on the ideXlab platform.
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tarp γ 2 and γ 8 differentially control ampar density across schaffer collateral commissural Synapses in the hippocampal ca1 area
The Journal of Neuroscience, 2016Co-Authors: Miwako Yamasaki, Kenji Sakimura, Masahiro Fukaya, Maya Yamazaki, Hirotsugu Azechi, Rie Natsume, Manabu Abe, Masahiko WatanabeAbstract:The number of AMPA-type glutamate receptors (AMPARs) at Synapses is the major determinant of synaptic strength and varies from synapse to synapse. To clarify the underlying molecular mechanisms, the density of AMPARs, PSD-95, and transmembrane AMPAR regulatory proteins (TARPs) were compared at Schaffer collateral/commissural (SCC) Synapses in the adult mouse hippocampal CA1 by quantitative immunogold electron microscopy using serial sections. We examined four types of SCC Synapses: perforated and nonperforated Synapses on pyramidal cells and axodendritic Synapses on parvalbumin-positive (PV synapse) and pravalbumin-negative interneurons (non-PV synapse). SCC Synapses were categorized into those expressing high-density (perforated and PV Synapses) or low-density (nonperforated and non-PV Synapses) AMPARs. Although the density of PSD-95 labeling was fairly constant, the density and composition of TARP isoforms was highly variable depending on the synapse type. Of the three TARPs expressed in hippocampal neurons, the disparity in TARP γ-2 labeling was closely related to that of AMPAR labeling. Importantly, AMPAR density was significantly reduced at perforated and PV Synapses in TARP γ-2-knock-out (KO) mice, resulting in a virtual loss of AMPAR disparity among SCC Synapses. In comparison, TARP γ-8 was the only TARP expressed at nonperforated Synapses, where AMPAR labeling further decreased to a background level in TARP γ-8-KO mice. These results show that synaptic inclusion of TARP γ-2 potently increases AMPAR expression and transforms low-density Synapses into high-density ones, whereas TARP γ-8 is essential for low-density or basal expression of AMPARs at nonperforated Synapses. Therefore, these TARPs are critically involved in AMPAR density control at SCC Synapses. SIGNIFICANCE STATEMENT Although converging evidence implicates the importance of transmembrane AMPA-type glutamate receptor (AMPAR) regulatory proteins (TARPs) in AMPAR stabilization during basal transmission and synaptic plasticity, how they control large disparities in AMPAR numbers or densities across central Synapses remains largely unknown. We compared the density of AMPARs with that of TARPs among four types of Schaffer collateral/commissural (SCC) hippocampal Synapses in wild-type and TARP-knock-out mice. We show that the density of AMPARs correlates with that of TARP γ-2 across SCC Synapses and its high expression is linked to high-density AMPAR expression at perforated type of pyramidal cell Synapses and Synapses on parvalbumin-positive interneurons. In comparison, TARP γ-8 is the only TARP expressed at nonperforated type of pyramidal cell Synapses, playing an essential role in low-density or basal AMPAR expression.
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dopamine synapse is a neuroligin 2 mediated contact between dopaminergic presynaptic and gabaergic postsynaptic structures
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Motokazu Uchigashima, Toshihisa Ohtsuka, Kazuto Kobayashi, Masahiko WatanabeAbstract:Midbrain dopamine neurons project densely to the striatum and form so-called dopamine Synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine Synapses, it remains unclear how dopamine Synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine Synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine Synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine Synapses coupled with a reciprocal increase of GABAergic Synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine Synapses over conventional GABAergic Synapses. Considering that MSN dendrites are preferential targets of dopamine Synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets.
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input specific intrasynaptic arrangements of ionotropic glutamate receptors and their impact on postsynaptic responses
The Journal of Neuroscience, 2009Co-Authors: Etsuko Tarusawa, Masahiko Watanabe, Yugo Fukazawa, Elek Molnar, Ko Matsui, Timotheus Budisantoso, Minoru Matsui, Ryuichi ShigemotoAbstract:To examine the intrasynaptic arrangement of postsynaptic receptors in relation to the functional role of the synapse, we quantitatively analyzed the two-dimensional distribution of AMPA and NMDA receptors (AMPARs and NMDARs, respectively) using SDS-digested freeze-fracture replica labeling (SDS-FRL) and assessed the implication of distribution differences on the postsynaptic responses by simulation. In the dorsal lateral geniculate nucleus, corticogeniculate (CG) Synapses were twice as large as retinogeniculate (RG) Synapses but expressed similar numbers of AMPARs. Two-dimensional views of replicas revealed that AMPARs form microclusters in both Synapses to a similar extent, resulting in larger AMPAR-lacking areas in the CG Synapses. Despite the broad difference in the AMPAR distribution within a synapse, our simulations based on the actual receptor distributions suggested that the AMPAR quantal response at individual RG Synapses is only slightly larger in amplitude, less variable, and faster in kinetics than that at CG Synapses having a similar number of the receptors. NMDARs at the CG Synapses were expressed twice as many as those in the RG Synapses. Electrophysiological recordings confirmed a larger contribution of NMDAR relative to AMPAR-mediated responses in CG Synapses. We conclude that synapse size and the density and distribution of receptors have minor influences on quantal responses and that the number of receptors acts as a predominant postsynaptic determinant of the synaptic strength mediated by both the AMPARs and NMDARs.
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influence of parallel fiber purkinje cell synapse formation on postnatal development of climbing fiber purkinje cell Synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Takayuki Yoshida, Masayoshi Mishina, Masahiko Watanabe, Masanobu KanoAbstract:Abstract The climbing fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with “hypogranular” cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel fibers (PFs), and normal formation of PF–PC Synapses. Our understanding of how PF–PC synapse formation affects development of CF–PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor δ2 subunit (GluRδ2), an orphan receptor expressed selectively in PCs. Deletion of GluRδ2 results in impairment of PF–PC synapse formation, which leads to defects in development of CF–PC Synapses. In this article, we review how impaired PF–PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRδ2 knockout mice. We propose a new scheme that CF–PC Synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, “early phase” of CF synapse elimination from P7 to around P11, and “late phase” of CF synapse elimination from around P12. Normal PF–PC synapse formation is required for the “late phase” of CF synapse elimination.
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influence of parallel fiber purkinje cell synapse formation on postnatal development of climbing fiber purkinje cell Synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Masayoshi Mishina, Masahiko Watanabe, Masanobu Kano, Tomoyuki YoshidaAbstract:The climbing fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with "hypogranular" cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel fibers (PFs), and normal formation of PF-PC Synapses. Our understanding of how PF-PC synapse formation affects development of CF-PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in impairment of PF-PC synapse formation, which leads to defects in development of CF-PC Synapses. In this article, we review how impaired PF-PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout mice. We propose a new scheme that CF-PC Synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, "early phase" of CF synapse elimination from P7 to around P11, and "late phase" of CF synapse elimination from around P12. Normal PF-PC synapse formation is required for the "late phase" of CF synapse elimination.
Fekrije Selimi - One of the best experts on this subject based on the ideXlab platform.
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proteomic studies of a single cns synapse type the parallel fiber purkinje cell synapse
PLOS Biology, 2009Co-Authors: Fekrije Selimi, Ileana M Cristea, Elizabeth A Heller, Brian T Chait, Nathaniel HeintzAbstract:Precise neuronal networks underlie normal brain function and require distinct classes of synaptic connections. Although it has been shown that certain individual proteins can localize to different classes of Synapses, the biochemical composition of specific synapse types is not known. Here, we have used a combination of genetically engineered mice, affinity purification, and mass spectrometry to profile proteins at parallel fiber/Purkinje cell Synapses. We identify approximately 60 candidate postsynaptic proteins that can be classified into 11 functional categories. Proteins involved in phospholipid metabolism and signaling, such as the protein kinase MRCKγ, are major unrecognized components of this synapse type. We demonstrate that MRCKγ can modulate maturation of dendritic spines in cultured cortical neurons, and that it is localized specifically to parallel fiber/Purkinje cell Synapses in vivo. Our data identify a novel synapse-specific signaling pathway, and provide an approach for detailed investigations of the biochemical complexity of central nervous system synapse types.
Ryuichi Shigemoto - One of the best experts on this subject based on the ideXlab platform.
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target and input dependent organization of ampa and nmda receptors in synaptic connections of the cochlear nucleus
The Journal of Comparative Neurology, 2014Co-Authors: Maria E Rubio, Yugo Fukazawa, Naomi Kamasawa, Cheryl Clarkson, Elek Molnar, Ryuichi ShigemotoAbstract:We examined the synaptic structure, quantity and distribution of AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory Synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN Synapses on bushy cells (AN-BC Synapses) and fusiform cells (AN-FC Synapses) and PF Synapses on FC (PF-FC Synapses) and cartwheel cell spines (PF-CwC Synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF Synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC Synapses were the smallest and had the most densely packed IMPs, whereas the PF-CwC Synapses were the largest and had sparsely-packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intra-synapse-type relationship for glutamatergic Synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN Synapses, PF Synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF Synapses.
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target and input dependent organization of ampa and nmda receptors in synaptic connections of the cochlear nucleus
The Journal of Comparative Neurology, 2014Co-Authors: Maria E Rubio, Yugo Fukazawa, Naomi Kamasawa, Cheryl Clarkson, Elek Molnar, Ryuichi ShigemotoAbstract:We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory Synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN Synapses on bushy cells (AN-BC Synapses) and fusiform cells (AN-FC Synapses) and PF Synapses on FC (PF-FC Synapses) and cartwheel cell spines (PF-CwC Synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF Synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC Synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC Synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intrasynapse-type relationship for glutamatergic Synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN Synapses; PF Synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF Synapses.
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input specific intrasynaptic arrangements of ionotropic glutamate receptors and their impact on postsynaptic responses
The Journal of Neuroscience, 2009Co-Authors: Etsuko Tarusawa, Masahiko Watanabe, Yugo Fukazawa, Elek Molnar, Ko Matsui, Timotheus Budisantoso, Minoru Matsui, Ryuichi ShigemotoAbstract:To examine the intrasynaptic arrangement of postsynaptic receptors in relation to the functional role of the synapse, we quantitatively analyzed the two-dimensional distribution of AMPA and NMDA receptors (AMPARs and NMDARs, respectively) using SDS-digested freeze-fracture replica labeling (SDS-FRL) and assessed the implication of distribution differences on the postsynaptic responses by simulation. In the dorsal lateral geniculate nucleus, corticogeniculate (CG) Synapses were twice as large as retinogeniculate (RG) Synapses but expressed similar numbers of AMPARs. Two-dimensional views of replicas revealed that AMPARs form microclusters in both Synapses to a similar extent, resulting in larger AMPAR-lacking areas in the CG Synapses. Despite the broad difference in the AMPAR distribution within a synapse, our simulations based on the actual receptor distributions suggested that the AMPAR quantal response at individual RG Synapses is only slightly larger in amplitude, less variable, and faster in kinetics than that at CG Synapses having a similar number of the receptors. NMDARs at the CG Synapses were expressed twice as many as those in the RG Synapses. Electrophysiological recordings confirmed a larger contribution of NMDAR relative to AMPAR-mediated responses in CG Synapses. We conclude that synapse size and the density and distribution of receptors have minor influences on quantal responses and that the number of receptors acts as a predominant postsynaptic determinant of the synaptic strength mediated by both the AMPARs and NMDARs.
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number and density of ampa receptors in individual Synapses in the rat cerebellum as revealed by sds digested freeze fracture replica labeling
The Journal of Neuroscience, 2007Co-Authors: Miwako Masugitokita, Masahiko Watanabe, Elek Molnar, Etsuko Tarusawa, Kazushi Fujimoto, Ryuichi ShigemotoAbstract:The number of AMPA receptor (AMPAR) is the major determinant of synaptic strength at glutamatergic Synapses, but little is known about the absolute number and density of AMPARs in individual Synapses. Using SDS-digested freeze-fracture replica labeling, which has high detection efficiency comparable with electrophysiological noise analysis for functional AMPAR, we analyzed three kinds of excitatory Synapses in the molecular layer of the adult rat cerebellum. In parallel fiber (PF)–Purkinje cell (PC) Synapses, we found large variability in the number (38.1 ± 34.4 particles per synapse, mean ± SD; range, 2–178 particles per synapse) and density (437 ± 277 particles/μm 2 ; range, 48–1210 particles/μm 2 ) of immunogold-labeled AMPARs. Two-dimensional view and high sensitivity of this method revealed irregular-shaped small AMPAR clusters within Synapses. Climbing fiber (CF)–PC Synapses had higher number of AMPAR labeling (68.6 ± 34.5 particles per synapse) than PF–PC and PF–interneuron Synapses (36.8 ± 14.4 particles per synapse). Furthermore, AMPAR density at CF–PC and PF–interneuron Synapses was approximately five times higher and more uniform than that at PF–PC Synapses. These results suggest input- and target-dependent regulation of AMPAR-mediated synaptic strength.
Susan R. Sesack - One of the best experts on this subject based on the ideXlab platform.
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ultrastructural analysis of prefrontal cortical inputs to the rat amygdala spatial relationships to presumed dopamine axons and d1 and d2 receptors
Brain Structure & Function, 2008Co-Authors: Aline Pinto, Susan R. SesackAbstract:Projections from the prefrontal cortex (PFC) to the amygdala (AMG) regulate affective behaviors in a manner that is modulated by dopamine (DA). Although PFC and DA inputs overlap within the basolateral nucleus (BLA) and intercalated cell masses (ICMs), the spatial relationship between these afferents has not been investigated, nor is it known how DA D1 (D1R) and D2 (D2R) receptors are localized in relationship to PFC terminals. We therefore combined tract-tracing from the rat PFC to the AMG with immunocytochemical labeling of tyrosine hydroxylase (TH) to identify presumed DA axons or D1R and D2R. In both the ICMs and BLA, PFC terminals formed asymmetric Synapses onto spines that typically did not receive secondary synaptic inputs. TH-immunoreactive (-ir) fibers in the adjacent neuropil typically contacted different structures. Although PFC and TH-ir axons were sometimes apposed to the same dendrites or to each other, PFC terminals only rarely synapsed onto dendrites that also received Synapses from TH-ir axons. D1R-ir spines and dendrites were observed commonly within the ICMs but less frequently within the BLA, and PFC axons in the ICMs occasionally synapsed onto D1R-ir spines. Within both regions, D2R-ir spines, dendrites, and axons were observed. PFC terminals occasionally contained presynaptic labeling for D2R but were not observed to synapse onto D2R-ir targets. The infrequent observation of synaptic convergence between PFC and presumed DA terminals within the AMG suggests that DA modulates PFC inputs primarily via extrasynaptic mechanisms, a conclusion supported by the localization of D2R within and D1R postsynaptic to PFC terminals.
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prefrontal cortical projections to the rat dorsal raphe nucleus ultrastructural features and associations with serotonin and γ aminobutyric acid neurons
The Journal of Comparative Neurology, 2004Co-Authors: Michael P Jankowski, Susan R. SesackAbstract:Studies of human brain indicate that both the ventromedial prefrontal cortex (PFC) and the dorsal raphe nucleus (DRN) may be dysfunctional in major depressive illness, making it important to understand the functional interactions between these brain regions. Anatomical studies have shown that the PFC projects to the DRN, although the synaptic targets of this excitatory pathway have not yet been identified. Electrophysiological investigations in the rat DRN report that most serotonin neurons are inhibited by electrical stimulation of the PFC, suggesting that this pathway is more likely to synapse onto neighboring γ-aminobutyric acid (GABA) neurons than onto serotonin cells. We tested this hypothesis by electron microscopic examination of DRN sections dually labeled for biotin dextran amine anterogradely transported from the PFC and immunogold-silver labeling for tryptophan hydroxylase (TrH) or for GABA. In the DRN, the majority of PFC axons either synapsed onto unlabeled dendrites or failed to form detectable Synapses in single sections. Other PFC axons synapsed onto either TrH- or GABA-immunolabeled processes. Considerably more tissue sampling was necessary to detect PFC Synapses onto TrH- than onto GABA-labeled dendrites, suggesting that the latter connections are more common. In other cases, PFC terminals and TrH- or GABA-immunoreactive dendrites either were closely apposed, without forming detectable Synapses, or were separated by glial processes. These results provide potential anatomical substrates whereby the PFC can both directly and indirectly regulate the activity of serotonin neurons in the DRN and possibly contribute to the pathophysiology of depression. J. Comp. Neurol. 468:518–529, 2004. © 2003 Wiley-Liss, Inc.
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prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area
The Journal of Comparative Neurology, 1992Co-Authors: Susan R. Sesack, Virginia M. PickelAbstract:Physiological and pharmacological studies indicate that descending projections from the prefrontal cortex modulate dopaminergic transmission in the nucleus accumbens septi and ventral tegmental area. We investigated the ultrastructural bases for these interactions in rat by examining the synaptic associations between prefrontal cortical terminals labeled with anterograde markers (lesion-induced degeneration or transport of Phaseolus vulgaris leucoagglutinin; PHA-L) and neuronal processes containing immunoreactivity for the catecholamine synthesizing enzyme, tryosine hydroxylase. Prefrontal cortical terminals in the nucleus accumbens and ventral tegmental area contained clear, round vesicles and formed primarily asymmetric Synapses on spines or small dendrites. In the ventral tegmental area, these terminals also formed asymmetric Synapses on large dendrites and a few symmetric axodendritic Synapses. In the nucleus accumbens septi, degenerating prefrontal cortical terminals synapsed on spiny dendrites which received convergent input from terminals containing peroxidase immunoreactivity for tyrosine hydroxylase, or from unlabeled terminals. In single sections, some tyrosine hydroxylase-labeled terminals formed thin and punctate symmetric Synapses with dendritic shafts, or the heads and necks of spines. Close appositions, but not axo-axonic Synapses, were frequently observed between degenerating prefrontal cortical afferents and tyrosine hydroxylase-labeled or unlabeled terminals. In the ventral tegmental area, prefrontal cortical terminals labeled with immunoperoxidase for PHA-L were in synaptic contact with dendrites containing immunogold reaction product for tyrosine hydroxylase, or with unlabeled dendrites. These results suggest that: (1) catecholaminergic (mainly dopaminergic) and prefrontal cortical terminals in the nucleus accumbens septi dually synapse on common spiny neurons; and (2) dopaminergic neurons in the ventral tegmental area receive monosynaptic input from prefrontal cortical afferents. This study provides the first ultrastructural basis for multiple sites of cellular interaction between prefrontal cortical efferents and mesolimbic dopaminergic neurons.
