Researcher Database

Haruyuki Kamiya
Faculty of Medicine Interdisciplinary Medicine Department of Medical Biology
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Medicine Interdisciplinary Medicine Department of Medical Biology

Job Title

  • Professor

Research funding number

  • 10194979

J-Global ID

Research Interests

  • 軸索   シナプス   可塑性   グルタミン酸   海馬   

Research Areas

  • Life sciences / Physiology
  • Life sciences / Nervous system function

Academic & Professional Experience

  • 2004 - Today 北海道大学 医学研究科/研究院 教授
  • 2000 - 2004 神戸大学 医学系研究科 助教授
  • 1996 - 2000 Gunma University Faculty of Medicine
  • 1994 - 1996 Kanazawa University
  • 1987 - 1994 Kanazawa University

Association Memberships

  • SOCIETY FOR NEUROSCIENCE   THE JAPAN NEUROSCIENCE SOCIETY   PHYSIOLOGICAL SOCIETY OF JAPAN   

Research Activities

Published Papers

  • Frontiers in Cellular Neuroscience 2019/08 [Refereed][Not invited]
  • Kamiya H
    Frontiers in Cellular Neuroscience 2019/05 [Refereed][Not invited]
  • Hasegawa K, Kamiya H, Morimoto Y
    Biomedical research (Tokyo, Japan) 39 (5) 223 - 230 0388-6107 2018 [Refereed][Not invited]
  • Shunsuke Ohura, Haruyuki Kamiya
    eNeuro 5 (1) 2373-2822 2018/01/01 [Refereed][Not invited]
     
    Axonal spike is an important upstream process of transmitter release, which directly impacts on release probability from the presynaptic terminals. Despite the functional significance, possible activity-dependent modulation of axonal spikes has not been studied extensively, partly due to inaccessibility of the small structures of axons for electrophysiological recordings. In this study, we tested the possibility of use-dependent changes in axonal spikes at the hippocampal mossy fibers, where direct recordings from the axon terminals are readily feasible. Hippocampal slices were made from mice of either sex, and loose-patch clamp recordings were obtained from the visually identified giant mossy fiber boutons located in the stratum lucidum of the CA3 region. Stimulation of the granule cell layer of the dentate gyrus elicited axonal spikes at the single bouton which occurred in all or none fashion. Unexpected from the digital nature of spike signaling, the peak amplitude of the second spikes in response to paired stimuli at a 50-ms interval was slightly but reproducibly smaller than the first spikes. Repetitive stimuli at 20 or 100 Hz also caused progressive use-dependent depression during the train. Notably, veratridine, an inhibitor of inactivation of sodium channels, significantly accelerated the depression with minimal effect on the initial spikes. These results suggest that sodium channels contribute to use-dependent depression of axonal spikes at the hippocampal mossy fibers, possibly by shaping the afterdepolarization (ADP) following axonal spikes. Prolonged depolarization during ADP may inactivate a fraction of sodium channels and thereby suppresses the subsequent spikes at the hippocampal mossy fibers.
  • Koji Hoshino, Kan Hasegawa, Haruyuki Kamiya, Yuji Morimoto
    BIOMEDICAL RESEARCH-TOKYO 38 (3) 183 - 188 0388-6107 2017 [Refereed][Not invited]
     
    Interleukin-1 beta (IL-1 beta) is a key molecule in the inflammatory responses elicited during infection and injury. It exerts local effects on synaptic plasticity by binding to IL-1 receptors that are expressed at high levels in the hippocampus. We examined the effects of IL-1 beta on synaptic plasticity in different hippocampal regions in acute mouse brain slices by measuring long-term potentiation (LTP). IL-1 beta (1 ng/mL) was applied for 30 min before LTP was induced with high-frequency stimulation (HFS). LTP was significantly impaired by either IL-1 beta application to the Schaffer collateral- CA1 synapses or the associational/commissural (A/C) fiber-CA3 synapses, which are both dependent on N-methyl-D-aspartate (NMDA) receptor activation. However, mossy fiber-CA3 LTP, which is expressed presynaptically in an NMDA-independent manner, was not impaired by IL-1 beta. Our results demonstrate that IL-1 beta exerts variable effects on LTP at different kinds of synapses, indicating that IL-1 beta has synapse-specific effects on hippocampal synaptic plasticity.
  • Etsuko Suzukia, Haruyuki Kamiya
    NEUROSCIENCE RESEARCH 107 14 - 19 0168-0102 2016/06 [Refereed][Not invited]
     
    Kainate-type glutamate receptors (KARs) are the third class of ionotropic glutamate receptors whose activation leads to the unique roles in regulating synaptic transmission and circuit functions. In contrast to AMPA receptors (AMPARs), little is known about the mechanism of synaptic localization of KARs. PSD-95, a major scaffold protein of the postsynaptic density, is a candidate molecule that regulates the synaptic KARs. Although PSD-95 was shown to bind directly to KARs subunits, it has not been tested whether PSD-95 regulates synaptic KARs in intact synapses. Using PSD-95 knockout mice, we directly investigated the role of PSD-95 in the KARs-mediated components of synaptic transmission at hippocampal mossy fiber-CA3 synapse, one of the synapses with the highest density of KARs. Mossy fiber EPSCs consist of AMPA receptor (AMPAR)-mediated fast component and KAR-mediated slower component, and the ratio was significantly reduced in PSD-95 knockout mice. The size of KARs-mediated field EPSP reduced in comparison with the size of the fiber volley. Analysis of KARs-mediated miniature EPSCs also suggested reduced synaptic KARs. All the evidence supports critical roles of PSD-95 in regulating synaptic KARs. (C) 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
  • Shunsuke Ohura, Haruyuki Kamiya
    JOURNAL OF PHYSIOLOGICAL SCIENCES 66 (3) 189 - 196 1880-6546 2016/05 [Refereed][Not invited]
     
    The axon is a long neuronal process that originates from the soma and extends towards the presynaptic terminals. The pioneering studies on the squid giant axon or the spinal cord motoneuron established that the axon conducts action potentials faithfully to the presynaptic terminals with self-regenerative processes of membrane excitation. Recent studies challenged the notion that the fundamental understandings obtained from the study of squid giant axons are readily applicable to the axons in the mammalian central nervous system (CNS). These studies revealed that the functional and structural properties of the CNS axons are much more variable than previously thought. In this review article, we summarize the recent understandings of axon physiology in the mammalian CNS due to progress in the subcellular recording techniques which allow direct recordings from the axonal membranes, with emphasis on the hippocampal mossy fibers as a representative en passant axons typical for cortical axons.
  • Naoya Yamashita, Reina Aoki, Sandy Chen, Aoi Jitsuki-Takahashi, Shunsuke Ohura, Haruyuki Kamiya, Yoshio Goshima
    BRAIN RESEARCH 1631 127 - 136 0006-8993 2016/01 [Refereed][Not invited]
     
    Growing axons rely on local signaling at the growth cone for guidance cues. Semaphorin3A (Sema3A), a secreted repulsive axon guidance molecule, regulates synapse maturation and dendritic branching. We previously showed that local Sema3A signaling in the growth cones elicits retrograde retrograde signaling via PlexinA4 (PlexA4), one component of the Sema3A receptor, thereby regulating dendritic localization of AMPA receptor G1uA2 and proper dendritic development. In present study, we found that nimodipine (voltage-gated L-type Ca2+ channel blocker) and tetrodotoxin (TTX; voltage-gated Na+ channel blocker) suppress Sema3A-induced dendritic localization of GluA2 and dendritic branch formation in cultured hippocampal neurons. The local application of nimodipine or TTX to distal axons suppresses retrograde transport of Venus-Sema3A that has been exogenously applied to the distal axons. Sema3A facilitates axonal transport of PlexA4, which is also suppressed in neurons treated with either TTX or nimodipine. These data suggest that voltage-gated calcium and sodium channels mediate Sema3A retrograde signaling that regulates dendritic GluA2 localization and branch formation. (C) 2015 Elsevier B.V. All rights reserved.
  • Nobuyuki Obara, Haruyuki Kamiya, Satoshi Fukuda
    BIOMEDICAL RESEARCH-TOKYO 35 (1) 81 - 84 0388-6107 2014/02 [Refereed][Not invited]
     
    The inferior colliculus (IC) transmits the ascending auditory signal to the thalamic medial geniculate nucleus. Previous studies have reported that serotonergic input originating from the raphe nuclei has a strong influence on signal processing within the central nucleus of the IC. To identify the cellular target for the serotonergic modulation in the IC, we examined the effect of serotonin as well as selective. serotonin reuptake inhibitor (SSRI) fluvoxamine on spontaneous GABAergic and glycinergic inhibitory postsynaptic currents (sIPSCs) recorded with whole-cell recordings. Consistent with earlier studies, we confirmed that serotonin robustly enhanced the frequency, but not amplitude, of GABAergic sIPSCs. It should be noted that the application of fluvoxamine alone marginally increased the frequency of GABAergic sIPSCs. These findings suggest that serotonin is endogenously released even in slice preparations, and it negatively modulates the tone of activity of inhibitory neurons within IC. We also examined the effect of serotonin and fluvoxamine on glycinergic sIPSCs and found that serotonin has a significantly weaker effect on glycinergic sIPSCs than on GABAergic sIPSCs. The differential sensitivity of the GABAergic and glycinergic sIPSCs to serotonin implies that serotonergic input plays a specific role in auditory information processing. Moreover, it suggests that the serotonergic input may contribute to pathological conditions such as tinnitus.
  • Kamiya Haruyuki
    JOURNAL OF PHYSIOLOGICAL SCIENCES 63 S38  1880-6546 2013 [Refereed][Not invited]
  • Haruyuki Kamiya
    JOURNAL OF NEUROSCIENCE 32 (19) 6517 - 6524 0270-6474 2012/05 [Refereed][Not invited]
     
    Postsynaptic expression of AMPA-type glutamate receptors (AMPAR) is more mobile than previously thought. Much evidence suggests that AMPAR are delivered from intracellular reserved pools to postsynaptic sites in a constitutive, as well as activity-dependent manner by exocytosis, lateral diffusion, or diffusional trapping. These notions were supported by optical monitoring of AMPAR subunits labeled with macromolecular tags such as GFP or Immunobeads, although it remains uncertain whether the mode and rate of synaptic delivery are similar to native "unlabeled" receptors. To reveal the real-time dynamics of native AMPAR in situ, photochemical inactivation of surface receptors using 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX), a photoreactive AMPAR blocker, was adopted for acute hippocampal slices of mice. Because of the irreversible block due to cross-link formation between ANQX and surface AMPAR, recovery of EPSPs after photoinactivation reflects the time course of synaptic delivery of intracellular AMPAR. BriefUV illumination with fast application of ANQX resulted in persistent suppression of EPSPs for a prolonged period of up to 3 h, suggesting minimal synaptic delivery of AMPAR by exocytosis in the resting condition. Kinetic analysis of EPSP recovery clarified that the supply of postsynaptic AMPAR from the intracellular pool is dominated in the initial, but not in the later, phase of long-term potentiation (LTP). These results suggest that constitutive synaptic delivery is minimal in the resting condition at intact hippocampal synapses in a time scale of hours, while postsynaptic AMPAR are replaced with those in intracellular pools almost exclusively in an activity-dependent manner, typically shortly after LTP induction.
  • Takeshi Uchida, Satoshi Fukuda, Haruyuki Kamiya
    HIPPOCAMPUS 22 (2) 222 - 229 1050-9631 2012/02 [Refereed][Not invited]
     
    Several classes of ionotropic receptors have been reported to depolarize the axonal membrane of hippocampal mossy fibers. Both kainate receptors and GABAA receptors are localized on axons and/or presynaptic terminals, and these receptors have been known to be activated by synaptically released glutamate and GABA which spill out from the synaptic clefts. However the relative contribution of these two receptors in modulating the excitability of mossy fiber axon was not reported so far. In this study, we revealed that glutamate spilled out from commissural/associational synapses evoked the facilitation of antidromic population spikes of mossy fibers. Increase in amplitude and decrease in latency of population spikes suggest that the number of recruited mossy fibers increases by depolarization of axonal membrane. Application of non-NMDA receptor antagonist CNQX (10 mu M) almost abolished this effect. TBOA (30 mu M), an inhibitor of glutamate transporter, prolonged the duration of heterosynaptic facilitation. These results suggest that glutamate released from distant commissural/associational synapses spills out from synaptic cleft and activates the kainate receptors on the mossy fibers of CA3 region, and plays a major role in modulating presynaptic excitability than GABA. (C) 2010 Wiley Periodicals, Inc.
  • Ikuma Sato, Haruyuki Kamiya
    NEUROSCIENCE RESEARCH 71 (2) 183 - 187 0168-0102 2011/10 [Refereed][Not invited]
     
    Caffeine robustly enhances transmitter release from the hippocampal mossy fiber terminals, although it remains uncertain whether calcium mobilization through presynaptic ryanodine receptors mediates this enhancement. In this study, we adopted a selective adenosine A1 blocker to assess relative contribution of A1 receptors and ryanodine receptors in caffeine-induced synaptic enhancement. Application of caffeine further enhanced transmission at the hippocampal mossy fiber synapse even after full blockade of adenosine A1 receptors. This result suggests that caffeine enhances mossy fiber synaptic transmission by two distinct presynaptic mechanisms, i.e., removal of A1 receptor-mediated tonic inhibition and ryanodine receptor-mediated calcium release from intracellular stores. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
  • Haruyuki Kamiya
    NEUROSCIENCE RESEARCH 71 E322 - E322 0168-0102 2011 [Refereed][Not invited]
  • Haruyuki Kamiya
    JOURNAL OF PHYSIOLOGICAL SCIENCES 60 S84 - S84 1880-6546 2010 [Refereed][Not invited]
  • Kaori Akashi, Toshikazu Kakizaki, Haruyuki Kamiya, Masahiro Fukaya, Miwako Yamasaki, Manabu Abe, Rie Natsume, Masahiko Watanabe, Kenji Sakimura
    JOURNAL OF NEUROSCIENCE 29 (35) 10869 - 10882 0270-6474 2009/09 [Refereed][Not invited]
     
    GluN2B (GluR epsilon 2/NR2B) subunit is involved in synapse development, synaptic plasticity, and cognitive function. However, its roles in synaptic expression and function of NMDA receptors (NMDARs) in the brain remain mostly unknown because of the neonatal lethality of global knock-out mice. To address this, we generated conditional knock-out mice, in which GluN2B was ablated exclusively in hippocampal CA3 pyramidal cells. By immunohistochemistry, GluN2B disappeared and GluN1 (GluR zeta 1/NR1) was moderately reduced, whereas GluN2A (GluR epsilon 1/NR2A) and postsynaptic density-95 (PSD-95) were unaltered in the mutant CA3. This was consistent with protein contents in the CA3 crude fraction: 9.6% of control level for GluN2B, 47.7% for GluN1, 90.6% for GluN2A, and 98.0% for PSD-95. Despite the remaining NMDARs, NMDAR-mediated currents and long-term potentiation were virtually lost at various CA3 synapses. Then, we compared synaptic NMDARs by postembedding immunogold electron microscopy and immunoblot using the PSD fraction. In the mutant CA3, GluN1 was severely reduced in both immunogold (20.6-23.6%) and immunoblot (24.6%), whereas GluN2A and PSD-95 were unchanged in immunogold but markedly reduced in the PSD fraction (51.4 and 36.5%, respectively), indicating increased detergent solubility of PSD molecules. No such increased solubility was observed for GluN2B in the CA3 of GluN2A-knock-out mice. Furthermore, significant decreases were found in the ratio of filamentous to globular actin (49.5%) and in the density of dendritic spines (76.2%). These findings suggest that GluN2B is critically involved in NMDAR channel function, organization of postsynaptic macromolecular complexes, formation or maintenance of dendritic spines, and regulation of the actin cytoskeleton.
  • Takeshi Uchida, Satoshi Fukuda, Haruyuki Kamiya
    JOURNAL OF PHYSIOLOGICAL SCIENCES 59 233 - 233 1880-6546 2009 [Refereed][Not invited]
  • Kaori Akashi, Toshikazu Kakizaki, Haruyuki Kamiya, Masahiro Fukaya, Miwako Yamasaki, Manabu Abe, Masahiko Watanabe, Kenji Sakimura
    NEUROSCIENCE RESEARCH 65 S139 - S140 0168-0102 2009 [Refereed][Not invited]
  • Masataka Yaginuma, Haruyuki Kamiya
    JOURNAL OF PHYSIOLOGICAL SCIENCES 59 145 - 145 1880-6546 2009 [Refereed][Not invited]
  • Haruyuki Kamiya
    JOURNAL OF PHYSIOLOGICAL SCIENCES 59 236 - 236 1880-6546 2009 [Refereed][Not invited]
  • Ikuma Sato, Haruyuki Kamiya
    NEUROSCIENCE RESEARCH 65 S143 - S144 0168-0102 2009 [Refereed][Not invited]
  • Nobuyuki Obara, Satoshi Fukuda, Haruyuki Kamiya
    JOURNAL OF PHYSIOLOGICAL SCIENCES 59 137 - 137 1880-6546 2009 [Refereed][Not invited]
  • Haruyuki Kamiya
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 (45) E81 - E81 0027-8424 2008/11 [Refereed][Not invited]
  • Hidemi Shimizu, Masahiro Fukaya, Miwako Yamasaki, Masahiko Watanabe, Toshiya Manabe, Haruyuki Kamiya
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 (33) 11998 - 12003 0027-8424 2008/08 [Refereed][Not invited]
     
    Presynaptic Ca2+ stores have been suggested to regulate Ca2+ dynamics within the nerve terminals at certain types of the synapse. However, little is known about their mode of activation, molecular identity, and detailed subcellular localization. Here, we show that the ryanodine-sensitive stores exist in axons and amplify presynaptic Ca2+ accumulation at the hippocampal mossy fiber synapses, which display robust presynaptic forms of plasticity. Caffeine, a potent drug inducing Ca2+ release from ryanodine-sensitive stores, causes elevation of presynaptic Ca2+ levels and enhancement of transmitter release from the mossy fiber terminals. The blockers of ryanodine receptors, TMB-8 or ryanodine, reduce presynaptic Ca2+ transients elicited by repetitive stimuli of mossy fibers but do not affect those evoked by single shocks, suggesting that ryanodine receptors amplify presynaptic Ca2+ dynamics in an activity dependent manner. Furthermore, we generated the specific antibody against the type 2 ryanodine receptor (RyR2; originally referred to as the cardiac type) and examined the cellular and subcellular localization using immunohistochemistry. RyR2 is highly expressed in the stratum lucidum of the CA3 region and mostly colocalizes with axonal marker NF160 but not with terminal marker VGLUT1. Immunoelectron microscopy revealed that RyR2 is distributed around smooth ER within the mossy fibers but is almost excluded from their terminal portions. These results suggest that axonal localization of RyR2 at sites distant from the active zones enables use dependent Ca2+ release from intracellular stores within the mossy fibers and thereby facilitates robust presynaptic forms of plasticity at the mossy fiber-CA3 synapse.
  • Uchigashima M, Fukaya M, Watanabe M, Kamiya H
    The Journal of neuroscience : the official journal of the Society for Neuroscience 30 27 (30) 8088 - 8100 0270-6474 2007/07/25 [Refereed][Not invited]
  • Fumikazu Suto, Miu Tsuboi, Haruyuki Kamiya, Hidenobu Mizuno, Yuji Kiyama, Shoji Komai, Masayuki Shimizu, Makoto Sanbo, Takeshi Yagi, Yasushi Hiromi, Alain Chedotal, Kevin J. Mitchell, Toshiya Manabe, Hajime Fujisawa
    NEURON 53 (4) 535 - 547 0896-6273 2007/02 [Refereed][Not invited]
     
    Hippocampal mossy fibers project preferentially to the stratum lucidum, the proximal-most lamina of the suprapyramidal region of CA3. The molecular mechanisms that govern this lamina-restricted projection are still unknown. We examined the projection pattern of mossy fibers in mutant mice for semaphorin receptors plexin-A2 and plexin-A4, and their ligand, the transmembrane semaphorin Sema6A. We found that plexin-A2 deficiency causes a shift of mossy fibers from the suprapyramidal region to the infra- and intrapyramidal regions, while plexin-A4 deficiency induces inappropriate spreading of mossy fibers within CA3. We also report that the plexin-A2 loss-of-function phenotype is genetically suppressed by Sema-6A loss of function. Based on these results, we propose a model for the lamina-restricted projection of mossy fibers: the expression of plexinA4 on mossy fibers prevents them from entering the Sema6A-expressing suprapyramidal region of CA3 and restricts them to the proximal-most part, where Sema6A repulsive activity is attenuated by plexin-A2.
  • Haruyuki Kamiya
    NEUROSCIENCE RESEARCH 58 S13 - S13 0168-0102 2007 [Refereed][Not invited]
  • Masahiro Fukaya, Mika Tsujita, Maya Yamazaki, Etsuko Kushiya, Manabu Abe, Kaori Akashi, Rie Natsume, Masanobu Kano, Haruyuki Kamiya, Masahiko Watanabe, Kenji Sakimura
    EUROPEAN JOURNAL OF NEUROSCIENCE 24 (8) 2177 - 2190 0953-816X 2006/10 [Refereed][Not invited]
     
    Transmembrane alpha-amino-3-hydroxyl-5-isoxazolepropionate (AMPA) receptor regulatory proteins (TARPs) play pivotal roles in AMPA receptor trafficking and gating. Here we examined cellular and subcellular distribution of TARP gamma-8 in the mouse brain. Immunoblot and immunofluorescence revealed the highest concentration of gamma-8 in the hippocampus. Immunogold electron microscopy demonstrated dense distribution of gamma-8 on the synaptic and extrasynaptic surface of hippocampal neurons with very low intracellular labeling. Of the neuronal surface, gamma-8 was distributed at the highest level on asymmetrical synapses of pyramidal cells and interneurons, whereas their symmetrical synapses selectively lacked immunogold labeling. Then, the role of gamma-8 in AMPA receptor expression was pursued in the hippocampus using mutant mice defective in the gamma-8 gene. In the mutant cornu ammonis (CA)1 region, synaptic and extrasynaptic AMPA receptors on dendrites and spines were severely reduced to 35-37% of control levels, whereas reduction was mild for extrasynaptic receptors on somata (74%) and no significant decrease was seen for intracellular receptors within spines. In the mutant CA3 region, synaptic AMPA receptors were reduced mildly at asymmetrical synapses in the stratum radiatum (67% of control level), and showed no significant decrease at mossy fiber-CA3 synapses. Therefore, gamma-8 is abundantly distributed on hippocampal excitatory synapses and extrasynaptic membranes, and plays an important role in increasing the number of synaptic and extrasynaptic AMPA receptors on dendrites and spines, particularly, in the CA1 region. Variable degrees of reduction further suggest that other TARPs may also mediate this function at different potencies depending on hippocampal subregions, input sources and neuronal compartments.
  • Ayuko Sakane, Shinji Manabe, Hiroyoshi Ishizaki, Miki Tanaka-Okamoto, Emi Kiyokage, Kazunori Toida, Takayuki Yoshida, Jun Miyoshi, Haruyuki Kamiya, Yoshimi Takai, Takuya Sasaki
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 103 (26) 10029 - 10034 0027-8424 2006/06 [Refereed][Not invited]
     
    Rab3A small G protein is a member of the Rab family and is most abundant in the brain, where it is localized on synaptic vesicles. Evidence is accumulating that Rab3A plays a key role in neurotransmitter release and synaptic plasticity. Rab3A cycles between the GDP-bound inactive and GTP-bound active forms, and this change in activity is associated with the trafficking cycle of synaptic vesicles at nerve terminals. Rab3 GTPase-activating protein (GAP) stimulates the GTPase activity of Rab3A and is expected to determine the timing of the dissociation of Rab3A from synaptic vesicles, which may be coupled with synaptic vesicle exocytosis. Rab3 GAP consists of two subunits: the catalytic subunit p130 and the noncatalytic subunit p150. Recently, mutations in p130 were found to cause Warburg Micro syndrome with severe mental retardation. Here, we generated p130-deficient mice and found that the GTP-bound form of Rab3A accumulated in the brain. Loss of p130 in mice resulted in inhibition of Ca2+-dependent glutamate release from cerebrocortical synaptosomes and altered short-term plasticity in the hippocampal CA1 region. Thus, Rab3 GAP regulates synaptic transmission and plasticity by limiting the amount of the GTP-bound form of Rab3A.
  • T Yoshida, M Fukaya, M Uchigashima, E Miura, H Kamiya, M Kano, M Watanabe
    JOURNAL OF NEUROSCIENCE 26 (18) 4740 - 4751 0270-6474 2006/05 [Refereed][Not invited]
     
    2-Arachidonoyl-glycerol ( 2-AG) is an endocannabinoid that is released from postsynaptic neurons, acts retrogradely on presynaptic cannabinoid receptor CB1, and induces short- and long-term suppression of transmitter release. To understand the mechanisms of the 2-AG-mediated retrograde modulation, we investigated subcellular localization of a major 2-AG biosynthetic enzyme, diacylglycerol lipase-alpha( DAGL alpha), by using immunofluorescence and immunoelectron microscopy in the mouse brain. In the cerebellum, DAGL alpha was predominantly expressed in Purkinje cells. DAGL alpha was detected on the dendritic surface and occasionally on the somatic surface, with a distal-to-proximal gradient from spiny branchlets toward somata. DAGL alpha was highly concentrated at the base of spine neck and also accumulated with much lower density on somatodendritic membrane around the spine neck. However, DAGL alpha was excluded from the main body of spine neck and head. In hippocampal pyramidal cells, DAGL alpha was also accumulated in spines. In contrast to the distribution in Purkinje cells, DAGL alpha was distributed in the spine head, neck, or both, whereas somatodendritic membrane was labeled very weakly. These results indicate that DAGL alpha is essentially targeted to postsynaptic spines in cerebellar and hippocampal neurons, but its fine distribution within and around spines is differently regulated between the two neurons. The preferential spine targeting should enable efficient 2-AG production on excitatory synaptic activity and its swift retrograde modulation onto nearby presynaptic terminals expressing CB1. Furthermore, different fine localization within and around spines suggests that the distance between postsynaptic 2-AG production site and presynaptic CB1 is differentially controlled depending on neuron types.
  • Takayuki Yoshida, Masahiro Fukaya, Motokazu Uchigashima, Eriko Miura, Haruyuki Kamiya, Masanobu Kano, Masahiko Watanabe
    NEUROSCIENCE RESEARCH 55 S77 - S77 0168-0102 2006 [Refereed][Not invited]
  • Masahiro Fukaya, Mika Tsujita, Maya Yamazaki, Etsuko Kushiya, Manabu Abe, Kaori Akashi, Masanobu Kano, Haruyuki Kamiya, Kenji Sakimura, Masahiko Watanabe
    NEUROSCIENCE RESEARCH 55 S172 - S172 0168-0102 2006 [Refereed][Not invited]
  • F Nakatsu, M Okada, H Iwasa, G Zhu, Y Kasagi, F Mori, H Kamiya, A Harada, Shimoyama, I, K Wakabayashi, T Manabe, S Kaneko, S Yuasa, T Saito, H Ohno
    EPILEPSIA 46 67 - 68 0013-9580 2005 [Refereed][Not invited]
  • F Nakatsu, M Okada, F Mori, N Kumazawa, H Iwasa, G Zhu, Y Kasagi, H Kamiya, A Harada, K Nishimura, A Takeuchi, T Miyazaki, M Watanabe, S Yuasa, T Manabe, K Wakabayashi, S Kaneko, T Saito, H Ohno
    MOLECULAR BIOLOGY OF THE CELL 15 221A - 221A 1059-1524 2004/11 [Refereed][Not invited]
  • F Nakatsu, M Okada, F Mori, N Kumazawa, H Iwasa, G Zhu, Y Kasagi, H Kamiya, A Harada, K Nishimura, A Takeuchi, T Miyazaki, M Watanabe, S Yuasa, T Manabe, K Wakabayashi, S Kaneko, T Saito, H Ohno
    JOURNAL OF CELL BIOLOGY 167 (2) 293 - 302 0021-9525 2004/10 [Refereed][Not invited]
     
    A P-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking mu3B, a subunit of AP-3B. mu3B(-/-) mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of gamma-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in mu3B(-/-) mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy.
  • Y Tabata, Y Ouchi, H Kamiya, T Manabe, K Arai, S Watanabe
    MOLECULAR AND CELLULAR BIOLOGY 24 (10) 4513 - 4521 0270-7306 2004/05 [Refereed][Not invited]
     
    With the goal of generating retinal cells from mouse embryonic stem (ES) cells by exogenous gene transfer, we introduced the Rx/rax transcription factor, which is expressed in immature retinal cells, into feeder-free mouse ES cells (CCE). CCE cells expressing Rx/rax as well as enhanced green fluorescent protein (CCE-RX/E cells) proliferated and remained in the undifferentiated state in the presence of leukemia inhibitory factor, as did parental ES cells. We made use of mouse embryo retinal explant cultures to address the differentiation ability of grafted ES cells. Dissociated embryoid bodies were treated with retinoic acid for use as donor cells and cocultured with retina explants for 2 weeks. In contrast to the parental CCE cells, which could not migrate into host retinal cultures, CCE-RX/E cells migrated into the host retina and extended their process-like structures between the host retinal cells. Most of the grafted CCE-RX/E cells became located in the ganglion cell and inner plexiform layers and expressed ganglion and horizontal cell markers. Furthermore, these grafted cells had the electrophysiological properties expected of ganglion cells. Our data thus suggest that subpopulations of retinal neurons can be generated in retinal explant cultures from grafted mouse ES cells ectopically expressing the transcription factor Rx/rax.
  • H Kamiya, K Umeda, S Ozawa, T Manabe
    JOURNAL OF NEUROSCIENCE 22 (24) 10524 - 10528 0270-6474 2002/12 [Refereed][Not invited]
     
    The hippocampal mossy fiber (MF)-CA3 synapse exhibits NMDA receptor-independent long-term potentiation (LTP), which is expressed by presynaptic mechanisms leading to persistent enhancement of transmitter release. Recent studies have identified several molecules that may play an important role in MF-LTR These include Rab3A, RIM1alpha, kainate autoreceptor, and hyperpolarization-activated cation channel (I-h). However, the precise cellular expression mechanism remains to be determined because some studies noticed essential roles of release machinery molecules, whereas others suggested modulation of the ionotropic processes affecting Ca2+ entry into the presynaptic terminals. Using fluorescence recordings of presynaptic Ca2+ in hippocampal slices, here we demonstrated that MF-LTP is not accompanied by an increase in presynaptic Ca2+ influx during an action potential. Whole-cell recordings from CA3 neurons revealed long-lasting increases in mean frequency, but not mean amplitude, of miniature EPSCs after the high-frequency stimulation of MFs. These data indicate that the presynaptic expression mechanisms responsible for enhanced transmitter release during MF-LTP involve persistent modification of presynaptic molecular targets residing downstream of Ca2+ entry.
  • H Kamiya, S Ozawa, T Manabe
    JOURNAL OF NEUROSCIENCE 22 (21) 9237 - 9243 0270-6474 2002/11 [Refereed][Not invited]
     
    Transmitter release at the hippocampal mossy fiber (MF)-CA3 synapse exhibits robust use-dependent short-term plasticity with an extremely wide dynamic range. Recent studies revealed that presynaptic kainate receptors (KARs), which specifically localized on the MF axons, mediate unusually large facilitation at this particular synapse in concert with the action of residual Ca2+. However, it is currently unclear how activation of kainate autoreceptors enhances transmitter release in an activity-dependent manner. Using fluorescence recordings of presynaptic Ca2+ and voltage in hippocampal slices, here we demonstrate that paired-pulse stimulation (with 20-200 msec intervals) resulted in facilitation of Ca2+ influx into the MF terminals, as opposed to other synapses, such as the Schaffer collateral-CA1 synapse. These observations deviate from typical residual Ca2+ hypothesis of facilitation, assuming an equal amount of Ca2+ influx per action potential. Pharmacological experiments reveal that the facilitation of presynaptic Ca2+ influx is mediated by activation of KARs. We also found that action potentials of MF axons are followed by prominent afterdepolarization, which is partly mediated by activation of KARs. Notably, the time course of the afterdepolarization approximates to that of the paired-pulse facilitation of Ca2+ influx, suggesting that these two processes are closely related to each other. These results suggest that the novel mechanism amplifying presynaptic Ca2+ influx may underlie the robust short-term synaptic plasticity at the MF-CA3 synapse in the hippocampus, and this process is mediated by KARs whose activation evokes prominent afterdepolarization of MF axons and thereby enhances action potential-driven Ca2+ influx into the presynaptic terminals.
  • H Kamiya
    NEUROSCIENCE RESEARCH 42 (1) 1 - 6 0168-0102 2002/01 [Refereed][Not invited]
     
    Kainate-type ionotropic glutamate receptors (KARs) distribute widely and heterogenously throughout the central nervous system (CNS). There is now increasing evidence showing that, in addition to conventional action to mediate postsynaptic excitation, KAR also exerts presynaptic action modulating the amount of transmitter release at certain synapses in the CNS. The mechanism and physiological function of presynaptic KARs have been studied most extensively at the hippocampal mossy fiber (MF)-CA3 synapse, one of the CNS regions where the highest density of KAR subunits is expressed. One unique feature of presynaptic KARs is that their activation modulates transmitter release bi-directionally; weak activation enhances glutamate release, while strong activation leads to inhibition. These findings may be explained by their possible ionotropic action leading to axonal depolarization, which in turn regulates several voltage-dependent channels involved in action potential-dependent Ca2+ entry processes. Furthermore, physiological activation of presynaptic KAR involves an activity-dependent process. Large frequency facilitation, a form of short-term plasticity characteristic of the MF-CA3 synapse, is mediated, at least partly, by presynaptic KAR. Bi-directional and activity-dependent regulation of transmitter release by kainate autoreceptors might have physiological significance in information processing in the hippocampus and other CNS regions, as well as its well-known pathological action contributing to epileptogenesis. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
  • H Ishizaki, J Miyoshi, H Kamiya, A Togawa, M Tanaka, T Sasaki, K Endo, A Mizoguchi, S Ozawa, Y Takai
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 97 (21) 11587 - 11592 0027-8424 2000/10 [Refereed][Not invited]
     
    Rab CDP dissociation inhibitor alpha (Rab GDl alpha) is a regulator of the Rab small G proteins implicated in neurotransmission, and mutations of Rab GDl alpha cause human X-linked mental retardation associated with epileptic seizures. In Rab GDl alpha-deficient mice, synaptic potentials in the CA1 region of the hippocampus displayed larger enhancement during repetitive stimulation, which was apparently opposite to the phenotype of Rab3A-deficient mice. Furthermore, the Rab GDl alpha-deficient mice showed hypersensitivity to bicuculline, an inducer of epileptic seizures. These results suggest that Rab GDl alpha plays a specialized role in Rab3A recycling to suppress hyperexcitability via modulation of presynaptic forms of plasticity.
  • H Kamiya, S Ozawa
    JOURNAL OF PHYSIOLOGY-LONDON 523 (3) 653 - 665 0022-3751 2000/03 [Refereed][Not invited]
     
    1. The presynaptic action of kainate (KA) receptor activation at the mossy fibre-CA3 synapse was examined using fluorescence measurement of presynaptic Ca2+ influx as well as electrophysiological recordings in mouse hippocampal slices. 2. Bath application of a low concentration (0.2 mu M) of KA reversibly increased the amplitude of presynaptic volley evoked by stimulation of mossy fibres to 146 +/- 6% of control (n = 6), whereas it reduced the field excitatory postsynaptic potential (EPSPs) to 30 +/- 4%. 3. The potentiating effect of KA on the presynaptic volleys was also observed in Ca2+-free solution, and was partly antagonized by (2S,4R)-4-methylglutamic acid (SYM 2081, 1 mu M), which selectively desensitizes KA receptors. 4. The antidromic population spike of dentate granule cells evoked by stimulation of mossy fibres was increased by application of 0.2 mu M KA to 160 +/- 10% of control (n = 6). Whole-cell current-clamp recordings revealed that the stimulus threshold for generating antidromic spikes recorded from a single granule cell was lowered by KA application. 5. Application of KA (0.2 mu M) suppressed presynaptic Ca2+ influx to 78 +/- 4% of control (n = 6), whereas the amplitude of the presynaptic volley was increased. 6. KA at 0.2 mu M reversibly suppressed excitatory postsynaptic currents (EPSCs) evoked by mossy fibre simulation to 38 +/- 9 % of control (n = 5). 7. These results suggest that KA receptor activation enhances the excitability of mossy fibres, probably via axonal depolarization, and reduces action potential-induced Ca2+ influx, thereby inhibiting mossy fibre EPSCs presynaptically. This: novel presynaptic inhibitory action of IIA at the mossy fibre-CA3 synapse may regulate the excitability of highly interconnected CA3 networks.
  • H Kamiya, S Ozawa
    JOURNAL OF PHYSIOLOGY-LONDON 518 (2) 497 - 506 0022-3751 1999/07 [Refereed][Not invited]
     
    1. To investigate mechanisms responsible fbr the presynaptic inhibitory action mediated by the axonal group II metabotropic glutamate receptor (mGluR) at the mossy fibre-CA3 synapse, we used a quantitative fluorescence measurement of prresynaptic Ca2+ in mouse hippocampal slices. 2. Bath application of the group II mGluR-specific agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 1 mu M) reversibly suppressed the presynaptic Ca2+ influx (to 55.2 +/- 4.6% of control, n = 5) as well as field EPSPs recorded simultaneously (to 3.1 +/- 2.0%). Presynaptic fibre volley was not affected by 1 mu M DCG-IV. 3. A quantitative analysis of the inhibition of presynaptic Ca2+ influx and field EPXP suggested that DCG-IV suppressed the field EPSP to a greater extent than would be expected if the suppression were solely due to a decrease in the presynaptic Ca2+ influx. 4. DCG-IV at 1 mu M suppressed the mean frequency (to 73.8 +/- 3.9% of control, n = 11), but not the mean amplitude (to 97.0 +/- 3.5%), of miniature EPSCs recorded from CA3 neurones using the whole-cell patch-clamp technique. 5. These results suggest that group II mGluR-mediated suppression is due both to a reduction of presynaptic Ca2+ influx and downregulation of the subsequent exocytotic machinery.
  • H Kamiya, S Ozawa
    JOURNAL OF PHYSIOLOGY-LONDON 509 (3) 833 - 845 0022-3751 1998/06 [Refereed][Not invited]
     
    1. The effect of a low concentration (1 mu M) of kainate (kainic acid; KA) on presynaptic calcium (Ca2+) influx at the Schaffer collateral-commissural (SCC) synapse was examined in rat hippocampal slices. 2. Following selective loading of the presynaptic terminals with the fluorescent Ca2+ indicator rhod-2 AM, transient increases in the presynaptic Ca2+ concentration (pre[Ca2+](t)) and field excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the SCC pathway were recorded simultaneously. 3. Bath application of 1 mu M KA reversibly suppressed field EPSPs and pre[Ca2+](t) to 37.7 +/- 4.0% and 72.9 +/- 2.4% of control, respectively. Excitatory postsynaptic currents (EPSCs) recorded with the use of the whole-cell patch-clamp technique were also suppressed by 1 mu M KA to 42.6 +/- 6.3 % of control. A quantitative analysis of the decreases in pre[Ca2+](t) and the amplitude of field EPSP during KA application suggests that KA inhibits transmission primarily by reducing the pre[Ca2+](t). 4. Consistent with a presynaptic site for these effects, paired-pulse facilitation (PPF) was enhanced by 1 mu M KA. 5. A substantial KA-induced suppression of NMDA receptor-mediated EPSPs was detected when AMPA receptors were blocked by the AMPA receptor-selective antagonist GYKI 52466 (100 mu M). 6. The suppressive effect of KA on field EPSPs and pre[Ca2+](t) was antagonized by the KA antagonist NS-102 (10 mu M). 7. These results suggest that the presynaptic inhibitory action of KA at the hippocampal CA1 synapse is primarily due to the inhibition of Ca2+ influx into the presynaptic terminals.
  • K Obokata, H Kamiya, S Ozawa
    NEUROSCIENCE RESEARCH 29 (2) 171 - 179 0168-0102 1997/10 [Refereed][Not invited]
     
    Protein kinase C (PKC) is present abundantly in the mammalian central nervous system, and is involved in a variety of neuronal functions. Phorbol esters mimic the role of diacylglycerol, the physiological activator of PKC. We examined effects of phorbol 12,13-diacetate (PDAc) on excitatory synaptic transmission in neurons in the dentate granule cell layer of rat hippocampal slices using the whole-cell patch clamp technique. Excitatory postsynaptic currents (EPSCs) evoked by stimulation of the perforant path (pp) consisted of AMPA and NMDA receptor-mediated components. The application of PDAc potentiated both components of the EPSC, but the effect was more pronounced on the NMDA component. The potentiating effect of PDAc on the NMDA component was dependent on the membrane potential, being most prominent at -31 and -51 mV. omega-Agatoxin-IVA, a P-type Ca2+ channel blocker, suppressed both AMPA and NMDA components to a similar extent by reducing transmitter release. However, when the PDAc-potentiated AMPA component was reduced to the control level by applying omega-agatoxin-IVA, a substantial potentiation on the NMDA component remained. These results suggest that the potentiation of the NMDA component of the EPSC by PDAc is caused partly by a postsynaptic mechanism in the dentate neurons. (C) 1997 Elsevier Science Ireland Ltd.

Conference Activities & Talks

MISC

Awards & Honors

  • 1999 日本生理学会 奨励賞
     
    受賞者: 神谷 温之

Research Grants & Projects

Educational Activities

Teaching Experience

  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Introduction to Basic Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 医学・生物学、留学生、英語
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Master's Thesis Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 脳スライス、電気生理学的測定、パッチクランプ
  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : ニューロン、シナプス、可塑性
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Basic Brain Science
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : ニューロン、シナプス、可塑性
  • 基盤医学研究Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Brain Science Research
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード :  神経回路、生命科学、方法論
  • 基盤医学研究Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Soft Matter Medical Engineering
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 生命科学院
    キーワード : 再生医学、臨床医学、入門
  • 医学総論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Brain Science Research
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 脳科学、講演、セミナー
  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : ニューロン、シナプス、可塑性
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • Dissertation Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 脳スライス、電気生理学的測定、パッチクランプ
  • 選択実習Ⅱ
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
  • Freshman Seminar
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 脳、神経回路、ニューロン
  • PhysiologyⅡ
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 神経生理、筋肉生理、脳神経科学
  • Freshman Seminar
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 脳科学、神経科学、認知科学、心理学、生物学、医学、薬学、保健科学、先端計測

Campus Position History

  • 2017年7月1日 
    2019年6月30日 
    評価室室員
  • 2019年7月1日 
    2021年6月30日 
    評価室室員

Position History

  • 2017年7月1日 
    2019年6月30日 
    評価室室員
  • 2019年7月1日 
    2021年6月30日 
    評価室室員


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