基本情報

所属

• 医学研究院　連携医学系部門　医生物学分野

職名

• 教授

学位

• 博士（医学）（金沢大学）

ホームページURL

http://neurobiology.html.xdomain.jp/

科研費研究者番号

• 10194979

ORCID ID

•  https://orcid.org/0000-0002-2618-3146

Researcher ID

• E-7199-2010

J-Global ID

• 200901026622382170

研究キーワード

• 軸索   シナプス   可塑性   グルタミン酸   海馬   

研究分野

• ライフサイエンス / 生理学
• ライフサイエンス / 神経機能学

担当教育組織

•  学士課程　医学部（医学科）
•  修士課程　医学院
•  博士課程　医学院

職歴

• 2004年 - 現在 北海道大学 医学研究科/研究院 教授
• 2000年 - 2004年 神戸大学 医学系研究科 助教授
• 1996年 - 2000年 群馬大学 医学部 講師
• 1994年 - 1996年 金沢大学 医学部 講師
• 1987年 - 1994年 金沢大学 医学部 助手

所属学協会

• 米国神経科学学会   日本神経科学学会   日本生理学会   

研究活動情報

論文

• Simulation test for impartment of use-dependent plasticity by inactivation of axonal potassium channels on hippocampal mossy fibers

  Fumeng Zheng, Haruyuki Kamiya

  Frontiers in Cellular Neuroscience 17 1154910  2023年04月26日 [査読有り]
  
• Modeling analysis of subthreshold voltage signaling along hippocampal mossy fiber axons

  Haruyuki Kamiya

  Frontiers in Cellular Neuroscience 16 2022年08月 [査読有り][招待有り]
   

  Axons are classically thought of as electrically well isolated from other parts of the neurons due to the shape of a long cable-like structure. In contrast to this classical view on axonal compartmentalization, recent studies revealed that subthreshold depolarization of soma and dendrite passively propagates to the axons for a substantial distance, as demonstrated in some experimentally accessible axons including hippocampal mossy fibers and cortical pyramidal cell axons. Passive propagation of subthreshold dendritic EPSPs to the axons, defined as EPreSPs (excitatory presynaptic potentials), has been demonstrated to affect transmitter release from the axon terminals. To further characterize and explore the functional significance of passive subthreshold voltage signaling along the axons, the model of EPreSPs along hippocampal mossy fibers, proposed by Alle and Geiger, was reconstructed on the NEURON simulator. To test the effect of EPreSPs on action potentials and transmitter release from the axon terminals, additional conductances were incorporated into the previous passive propagation model. These include the axonal sodium, potassium, and leak channels as well as presynaptic calcium channels composed of P/Q-, N-, and R-types, which are reconstructed from the properties of those recorded from mossy fiber boutons experimentally. In this revised model, the preceding subthreshold EPreSPs slightly reduced the action potential-evoked presynaptic calcium currents by a decrease in the amplitude of action potentials due to the slow depolarization. It should be mentioned that EPreSPs by themselves elicited small calcium currents during subthreshold depolarization through these high-voltage activated calcium channels. Since the previous experimental study by simultaneous pre and postsynaptic recordings demonstrated that EPreSPs enhanced action potential-evoked transmitter release from the mossy fiber terminals, it has been suggested that different mechanisms from the enhancement of action potential-evoked presynaptic calcium entry may involve enhanced transmitter release by EPreSP. Small calcium entry by subthreshold EPreSPs may enhance transmitter release from the mossy fiber terminals by acting as high-affinity calcium sensors for enhancing transmitter release. Another form of axonal subthreshold voltage signaling, GABA-EPreSPs elicited by a spillover of GABA from surrounding interneurons, was also explored. Functional consequences of the two modes of axonal subthreshold voltage signaling were discussed with the simulation results.
• Editorial: Axon Neurobiology: Fine-Scale Dynamics of Microstructure and Function

  Haruyuki Kamiya, Dominique Debanne

  Frontiers in Cellular Neuroscience 14 2020年09月 [査読有り][招待有り]
  
• Excitability Tuning of Axons by Afterdepolarization

  Haruyuki Kamiya

  Frontiers in Cellular Neuroscience 13 2019年09月 [査読有り][通常論文]
  
• Modeling analysis of axonal after potential at hippocampal mossy fibers

  Kamiya H

  Frontiers in Cellular Neuroscience 2019年05月 [査読有り][通常論文]
  
• Sodium channel–dependent and –independent mechanisms underlying axonal afterdepolarization at mouse hippocampal mossy fibers.

  Ohura S, Kamiya H

  eNeuro 5 4 2018年08月 [査読有り][通常論文]
  
• Sevoflurane inhibits presynaptic calcium influx without affecting presynaptic action potentials in hippocampal CA1 region.

  Hasegawa K, Kamiya H, Morimoto Y

  Biomedical research (Tokyo, Japan) 39 5 223 - 230 2018年 [査読有り][通常論文]
   

  Although diverse effects of volatile anesthetics have been investigated in various studies, the mechanisms of action of such anesthetics, especially sevoflurane, remain elusive. In contrast to their potent modulation of inhibitory synaptic transmission there is little information about their effects on excitatory transmission in the brain. In this study, we examined the effect of sevoflurane on the excitatory synaptic transmission at CA1 synapses in hippocampal slices of mice. Sevoflurane at 5% was mixed with 95% O2 and 5% CO2 and bubbled in artificial cerebral spinal fluid (0.69 mM). Extracellular recordings of the field excitatory postsynaptic potential (fEPSP) and presynaptic fiber volley (FV) were made at physiological temperature. In addition, fluorescent measurements of presynaptic Ca2+ transients were performed while simultaneously recording fEPSP. Application of sevoflurane reduced the amplitude of fEPSP (45 ± 8%, n = 5). This effect was accompanied by concurrent enhancement of the paired-pulse facilitation of fEPSP (127 ± 5%, n = 12), suggesting a possible presynaptic site of action of sevoflurane. The amplitude of FV was not significantly affected (102 ± 5%, n = 5). In contrast, fluorescent measurements revealed that presynaptic Ca2+ influx was suppressed by sevoflurane (69 ± 5%, n = 7), as was simultaneously recorded fEPSP (44 ± 5%, n = 7). Our results suggest that sevoflurane potently suppresses excitatory synaptic transmission via inhibition of presynaptic Ca2+ influx without affecting presynaptic action potentials.
• Short-term depression of axonal spikes at the mouse hippocampal mossy fibers and sodium channel-dependent modulation

  Shunsuke Ohura, Haruyuki Kamiya

  eNeuro 5 1 2018年01月01日 [査読有り][通常論文]
   

  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.
• Synapse-specific effects of IL-1β on long-term potentiation in the mouse hippocampus.

  Hoshino K, Hasegawa K, Kamiya H, Morimoto Y

  Biomedical research (Tokyo, Japan) 38 3 183 - 188 2017年 [査読有り][通常論文]
   

  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.
• PSD-95 regulates synaptic kainate receptors at mouse hippocampal mossy fiber-CA3 synapses

  Etsuko Suzukia, Haruyuki Kamiya

  NEUROSCIENCE RESEARCH 107 14 - 19 2016年06月 [査読有り][通常論文]
   

  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.
• Excitability tuning of axons in the central nervous system

  Shunsuke Ohura, Haruyuki Kamiya

  JOURNAL OF PHYSIOLOGICAL SCIENCES 66 3 189 - 196 2016年05月 [査読有り][通常論文]
   

  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.
• Voltage-gated calcium and sodium channels mediate Sema3A retrograde signaling that regulates dendritic development

  Naoya Yamashita, Reina Aoki, Sandy Chen, Aoi Jitsuki-Takahashi, Shunsuke Ohura, Haruyuki Kamiya, Yoshio Goshima

  BRAIN RESEARCH 1631 127 - 136 2016年01月 [査読有り][通常論文]
   

  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.
• Serotonergic modulation of inhibitory synaptic transmission in mouse inferior colliculus

  Nobuyuki Obara, Haruyuki Kamiya, Satoshi Fukuda

  BIOMEDICAL RESEARCH-TOKYO 35 1 81 - 84 2014年02月 [査読有り][通常論文]
   

  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.
• Photochemical approach for analysis of AMPA receptor dynamics

  Kamiya Haruyuki

  JOURNAL OF PHYSIOLOGICAL SCIENCES 63 S38  2013年 [査読有り][通常論文]
  
• Photochemical Inactivation Analysis of Temporal Dynamics of Postsynaptic Native AMPA Receptors in Hippocampal Slices

  Haruyuki Kamiya

  JOURNAL OF NEUROSCIENCE 32 19 6517 - 6524 2012年05月 [査読有り][通常論文]
   

  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.
• Heterosynaptic enhancement of the excitability of hippocampal mossy fibers by long-range spill-over of glutamate

  Takeshi Uchida, Satoshi Fukuda, Haruyuki Kamiya

  HIPPOCAMPUS 22 2 222 - 229 2012年02月 [査読有り][通常論文]
   

  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.
• Assessing the roles of presynaptic ryanodine receptors and adenosine receptors in caffeine-induced enhancement of hippocampal mossy fiber transmission

  Ikuma Sato, Haruyuki Kamiya

  NEUROSCIENCE RESEARCH 71 2 183 - 187 2011年10月 [査読有り][通常論文]
   

  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.
• Observation of hippocampal mossy fiber axons and terminals by single-terminal electroporation of fluorescent dye

  Haruyuki Kamiya

  NEUROSCIENCE RESEARCH 71 E322 - E322 2011年 [査読有り][通常論文]
  
• Irreversible photoinactivation of AMPA receptors in hippocampal slice

  Haruyuki Kamiya

  JOURNAL OF PHYSIOLOGICAL SCIENCES 60 S84 - S84 2010年 [査読有り][通常論文]
  
• NMDA Receptor GluN2B (GluR epsilon 2/NR2B) Subunit Is Crucial for Channel Function, Postsynaptic Macromolecular Organization, and Actin Cytoskeleton at Hippocampal CA3 Synapses

  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 2009年09月 [査読有り][通常論文]
   

  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.
• TETANIC STIMULATION OF COMMISSURAL ASSOCIATIONAL SYNAPSES MODULATES THE EXCITABILITY OF HIPPOCAMPAL MOSSY FIBERS

  Takeshi Uchida, Satoshi Fukuda, Haruyuki Kamiya

  JOURNAL OF PHYSIOLOGICAL SCIENCES 59 233 - 233 2009年 [査読有り][通常論文]
  
• GluR epsilon 2 subunit is crucial for NMDA receptor activity and regulation of postsynaptic macromolecular organization

  Kaori Akashi, Toshikazu Kakizaki, Haruyuki Kamiya, Masahiro Fukaya, Miwako Yamasaki, Manabu Abe, Masahiko Watanabe, Kenji Sakimura

  NEUROSCIENCE RESEARCH 65 S139 - S140 2009年 [査読有り][通常論文]
  
• CAFFEINE-INDUCED MODULATION OF ACTION POTENTIAL WAVEFORM AT THE HIPPOCAMPAL MOSSY FIBER AXONS

  Masataka Yaginuma, Haruyuki Kamiya

  JOURNAL OF PHYSIOLOGICAL SCIENCES 59 145 - 145 2009年 [査読有り][通常論文]
  
• BUMETANIDE-SENSITIVE AND -INSENSITIVE ACTIONS OF GABA(A) RECEPTORS ON THE EXCITABILITY OF THE HIPPOCAMPAL MOSSY FIBERS

  Haruyuki Kamiya

  JOURNAL OF PHYSIOLOGICAL SCIENCES 59 236 - 236 2009年 [査読有り][通常論文]
  
• Caffeine-induced synaptic enhancement under blockade of adenosine A1 receptors at the hippocampal mossy fiber synapse

  Ikuma Sato, Haruyuki Kamiya

  NEUROSCIENCE RESEARCH 65 S143 - S144 2009年 [査読有り][通常論文]
  
• COMMON SIGNALING MECHANISMS FOR LONG-TERM POTENTIATION AND DOPAMINE-INDUCED SYNAPTIC ENHANCEMENT AT THE HIPPOCAMPAL MOSSY FIBER SYNAPSES

  Nobuyuki Obara, Satoshi Fukuda, Haruyuki Kamiya

  JOURNAL OF PHYSIOLOGICAL SCIENCES 59 137 - 137 2009年 [査読有り][通常論文]
  
• Reply to Scott and Rusakov: Roles of presynaptic Ca2+ store at the hippocampal mossy fiber synapse

  Haruyuki Kamiya

  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 45 E81 - E81 2008年11月 [査読有り][通常論文]
  
• Use-dependent amplification of presynaptic Ca2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse

  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 2008年08月 [査読有り][通常論文]
   

  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.
• Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus.

  Uchigashima M, Fukaya M, Watanabe M, Kamiya H

  The Journal of neuroscience : the official journal of the Society for Neuroscience 27 30 8088 - 8100 30 2007年07月25日 [査読有り][通常論文]
  
• Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers

  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 2007年02月 [査読有り][通常論文]
   

  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.
• Calcium store and presynaptic plasticity in the hippocampus

  Haruyuki Kamiya

  NEUROSCIENCE RESEARCH 58 S13 - S13 2007年 [査読有り][通常論文]
  
• Abundant distribution of TARP gamma-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites

  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 2006年10月 [査読有り][通常論文]
   

  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.
• Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3

  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 2006年06月 [査読有り][通常論文]
   

  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.
• Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor

  T Yoshida, M Fukaya, M Uchigashima, E Miura, H Kamiya, M Kano, M Watanabe

  JOURNAL OF NEUROSCIENCE 26 18 4740 - 4751 2006年05月 [査読有り][通常論文]
   

  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.
• Spine targeting of endocannabinoid synthesizing enzyme, diacylglycerol lipase-alpha in the cerebllum and hippocampus

  Takayuki Yoshida, Masahiro Fukaya, Motokazu Uchigashima, Eriko Miura, Haruyuki Kamiya, Masanobu Kano, Masahiko Watanabe

  NEUROSCIENCE RESEARCH 55 S77 - S77 2006年 [査読有り][通常論文]
  
• Distribution of TARP Gamma-8 on hippocampal neurons and its key role in synaptic and extrasynaptic expression for AMPA receptors

  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 2006年 [査読有り][通常論文]
  
• Epileptic seizure in mice deficient in mu 3B subunit of AP-3B complex.

  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 2005年 [査読有り][通常論文]
  
• Possible involvement of AP-3B in VGAT-associated inhibitory synaptic function

  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 2004年11月 [査読有り][通常論文]
  
• Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor

  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 2004年10月 [査読有り][通常論文]
   

  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.
• 転写因子RX/raxの発現によるマウスES細胞の網膜亜集団への分化(Retinal fate specification of mouse embryonic stem cells by ectopic expression of Rx/rax,a homeobox gene)

  渡辺 すみ子, 田畑 陽子, 大内 靖夫, 神谷 温之, 真鍋 俊也, 新井 賢一

  神経化学 43 2-3 381 - 381 2004年08月
• Specification of the retinal fate of mouse embryonic stem cells by ectopic expression of Rx/Rax, a homeobox gene

  Y Tabata, Y Ouchi, H Kamiya, T Manabe, K Arai, S Watanabe

  MOLECULAR AND CELLULAR BIOLOGY 24 10 4513 - 4521 2004年05月 [査読有り][通常論文]
   

  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.
• Presynaptic Ca2+ entry is unchanged during hippocampal mossy fiber long-term potentiation

  H Kamiya, K Umeda, S Ozawa, T Manabe

  JOURNAL OF NEUROSCIENCE 22 24 10524 - 10528 2002年12月 [査読有り][通常論文]
   

  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.
• Kainate receptor-dependent short-term plasticity of presynaptic Ca2+ influx at the hippocampal mossy fiber synapses

  H Kamiya, S Ozawa, T Manabe

  JOURNAL OF NEUROSCIENCE 22 21 9237 - 9243 2002年11月 [査読有り][通常論文]
   

  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.
• シナプス前カイニン酸受容体を介する海馬苔状線維の後脱分極応答

  神谷 温之, 真鍋 俊也

  日本生理学雑誌 64 10 220 - 220 (一社)日本生理学会 2002年10月
• forskolinによるマウス海馬苔状線維の興奮性の増強

  梅田 和昌, 神谷 温之, 清原 壽一, 真鍋 俊也

  日本生理学雑誌 64 4 83 - 83 (一社)日本生理学会 2002年04月
• Kainate receptor-dependent presynaptic modulation and plasticity

  H Kamiya

  NEUROSCIENCE RESEARCH 42 1 1 - 6 2002年01月 [査読有り][通常論文]
   

  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.
• 神経系特異的AP-3B複合体・μ3B遺伝子欠損マウスの作成・解析

  中津 史, 湯浅 茂樹, 岩佐 博人, 神谷 温之, 真鍋 俊也, 齊藤 隆, 大野 博司

  日本細胞生物学会大会講演要旨集 54回 96 - 96 (一社)日本細胞生物学会 2001年05月
• Role of Rab GDP dissociation inhibitor alpha in regulating plasticity of hippocampal neurotransmission

  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 2000年10月 [査読有り][通常論文]
   

  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.
• Kainate receptor-mediated presynaptic inhibition at the mouse hippocampal mossy fibre synapse

  H Kamiya, S Ozawa

  JOURNAL OF PHYSIOLOGY-LONDON 523 3 653 - 665 2000年03月 [査読有り][通常論文]
   

  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.
• Dual mechanism for presynaptic modulation by axonal metabotropic glutamate receptor at the mouse mossy fibre-CA3 synapse

  H Kamiya, S Ozawa

  JOURNAL OF PHYSIOLOGY-LONDON 518 2 497 - 506 1999年07月 [査読有り][通常論文]
   

  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.
• Kainate receptor-mediated inhibition of presynaptic Ca2+ influx and EPSP in area CA1 of the rat hippocampus

  H Kamiya, S Ozawa

  JOURNAL OF PHYSIOLOGY-LONDON 509 3 833 - 845 1998年06月 [査読有り][通常論文]
   

  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.
• Differential effects of phorbol ester on AMPA and NMDA components of excitatory postsynaptic currents in dentate neurons of rat hippocampal slices

  K Obokata, H Kamiya, S Ozawa

  NEUROSCIENCE RESEARCH 29 2 171 - 179 1997年10月 [査読有り][通常論文]
   

  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.
• A metabotropic glutamate receptor agonist DCG-IV suppresses synaptic transmission at mossy fiber pathway of the guinea pig hippocampus

  Yoshino, M., Sawada, S., Yamamoto, C., Kamiya, H.

  Neuroscience Letters 207 1 1996年 [査読有り]
  
• Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fiber synapses

  KAMIYA H.

  J Physiol (Lond) 493 2 447 - 455 1996年 [査読有り]
  
• Suppression of presynaptic calcium influx by metabotropic glutamate receptor agonists in neonatal rat hippocampus

  Yoshino, M., Kamiya, H.

  Brain Research 695 2 1995年 [査読有り]
  
• Residual Ca and short-term synaptic plasticity

  KAMIYA H.

  Nature 371 6498 603 - 606 1994年10月 [査読有り]
  
• Long-lasting potentiation of synaptic transmission in the Schaffer collateral-commis-sural pathway of the guinea pig hippocampus by activation of postsynaptic N-methyl-D-aspartate receptor.

  KAMIYA H.

  Synapse 13 2 186 - 194 1993年 [査読有り]
  
• Enhancement of postsynaptic responsiveness during long-term potentiation of mossy fiber synapses in guinea pig hippocampus

  Yamamoto, C., Sawada, S., Kamiya, H.

  Neuroscience Letters 138 1 1992年 [査読有り]
  
• An empirical test for the reliability of quantal analysis based on Pascal statistics

  Kamiya, H., Sawada, S., Yamamoto, C.

  Journal of Neuroscience Methods 42 1-2 1992年 [査読有り]
  
• Persistent enhancement of transmitter release accompanying long-term potentiation in the guinea pig hippocampus

  KAMIYA H.

  Neuroscience Letters 130 2 259 - 262 1991年 [査読有り]
  
• Some pharmacological differences between hippocampal exitatory and inhibitory synapses in transmitter release: an in vitro study.

  KAMIYA H.

  Synapse 8 3 229 - 235 1991年 [査読有り]
  
• Quantal Components of the Synaptic Potential Induced in Hippocampal Neurons by Activation of Granule Cells, and the Effect of 2-Amino-4-phosphonobutyric Acid

  Yamamoto, C., Higashima, M., Sawada, S., Kamiya, H.

  Hippocampus 1 1 93 - 106 1991年 [査読有り]
  
• Amiloride suppresses the induction of long‐term potentiation in the mossy fiber pathway but not in the commissural/associational pathway of the hippocampal CA3 region

  Kamiya, H.

  Synapse 3 3 1989年 [査読有り]
  
• Simultaneous recording of presynaptic spikes and excitatory postsynaptic potentials from monosynaptically connected hippocampal neurons

  Sawada, S., Kamiya, H., Yamamoto, C.

  Neurosci. Lett. 103 1 34 - 38 1989年 [査読有り]
  
• Quantal analysis of synaptic plasticity in the hippocampus

  Yamamoto, C., Sawada, S., Kamiya, H.

  Biomedical Research 10 SUPPL. 2 1989年 [査読有り]
  
• Additive feature of long-term potentiation and phorbol ester-induced synaptic enhancement in the mossy fiber-CA3 synapse

  Kamiya, H., Sawada, S., Yamamoto, C.

  Experimental Neurology 102 3 1988年 [査読有り]
  
• Synthetic ω-conotoxin blocks synaptic transmission in the hippocampus in vitro

  Kamiya, H., Sawada, S., Yamamoto, C.

  Neuroscience Letters 91 1 1988年 [査読有り]
  

書籍

• Insights in Cellular Neurophysiology: 2021

  Cherubini, E, Tropea, D, Maffei, A (担当:分担執筆範囲:Kamiya H: Modeling analysis of subthreshold voltage signaling along hippocampal mossy fiber axons. pp.199-209)
  Frontiers Media SA 2022年11月
• Axon Neurobiology: Fine-Scale Dynamics of Microstructure and Function

  Haruyuki Kamiya, Dominique Debanne (担当:共編者(共編著者))
  Frontiers Media SA 2020年12月

講演・口頭発表等

• 軸索興奮性の活動依存的な制御機構  [招待講演]

  神谷温之

  第100回日本生理学会大会シンポジウム 2023年03月 シンポジウム・ワークショップパネル（公募）
• Computational test for the roles of potassium channel inactivation in short-term plasticity  [招待講演]

  Haruyuki Kamiya

  The 10th RIEC International Symposium on Brain Functions and Brain Computer 2023年02月 シンポジウム・ワークショップパネル（指名）
• 計算論的アプローチによる軸索の閾値下シグナルの解析  [招待講演]

  神谷 温之

  第99回日本生理学会大会シンポジウム 2022年03月 シンポジウム・ワークショップパネル（公募）
• Modeling subthreshold voltage signaling along axon in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 10th RIEC International Symposium on Brain Functions and Brain Computer 2022年02月 シンポジウム・ワークショップパネル（指名）
• 単一軸索における伝播と発振のサブセルラー解析  [招待講演]

  神谷温之

  第126回日本解剖学会総会･全国学術集会・第98回日本生理学会大会合同大会シンポジウム 2021年03月 シンポジウム・ワークショップパネル（公募）
• Dynamic tuning of axonal excitability in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 9th RIEC International Symposium on Brain Functions and Brain Computer 2020年12月 シンポジウム・ワークショップパネル（指名）
• 軸索スパイクの計算論的神経生物学  [招待講演]

  神谷温之

  第97回日本生理学会大会シンポジウム（誌上開催） 2020年03月 シンポジウム・ワークショップパネル（公募）
• Distal axon as a potential oscillator for network activities in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 8th RIEC International Symposium on Brain Functions and Brain Computer 2020年02月 シンポジウム・ワークショップパネル（指名）
• Dynamic control of spike signaling by axonal afterdepolarization  [招待講演]

  神谷 温之

  第96回日本生理学会大会シンポジウム / 9th FAOPS 2019年03月 シンポジウム・ワークショップパネル（公募）
• Short-term plasticity of axonal spike signaling in the hippocampus  [招待講演]

  Haruyuki Kamiya

  Zuckerfest: a celebration of the life and times of Bob Zucker 2019年03月 シンポジウム・ワークショップパネル（指名）
• Temporal integration of axonal spike signaling in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 7th RIEC International Symposium on Brain Functions and Brain Computer 2019年02月 シンポジウム・ワークショップパネル（指名）
• 軸索バーストとてんかん原性  [招待講演]

  神谷 温之

  第95回日本生理学会大会シンポジウム 2018年03月
• Local control of axonal excitability in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 6th RIEC International Symposium on Brain Functions and Brain Computer 2018年02月 シンポジウム・ワークショップパネル（指名）
• 海馬における軸索スパイクのアナログ制御  [招待講演]

  大浦 峻介, 神谷 温之

  第94回日本生理学会大会シンポジウム 2017年03月
• Noncannonical mode of burst firing originated from distal axon  [招待講演]

  Haruyuki Kamiya

  The 5th RIEC International Symposium on Brain Functions and Brain Computer 2017年02月 シンポジウム・ワークショップパネル（指名）
• カイニン酸受容体による海馬苔状線維の興奮性制御  [招待講演]

  神谷 温之

  第93回日本生理学会大会シンポジウム 2016年03月
• Modelling spike signalling in the hippocampal axons  [招待講演]

  Haruyuki Kamiya

  The 4th RIEC International Symposium on Brain Functions and Brain Computer 2016年02月 シンポジウム・ワークショップパネル（指名）
• Physiology of single CNS axon: rediscovery of analogue tuning of axonal spikes  [招待講演]

  Haruyuki Kamiya

  University of Bordeaux Neurocampus Seminar 2016年01月 公開講演，セミナー，チュートリアル，講習，講義等
• 軸索興奮性と活動電位伝播の調節  [招待講演]

  神谷 温之

  第38回日本神経科学学会大会ミニシンポジウム 2015年07月
• 軸索の神経生物学：膜興奮と伝播  [招待講演]

  神谷 温之

  第120回日本解剖学会総会･全国学術集会・第92回日本生理学会大会合同大会合同教育プログラム 教育講演 2015年03月
• 海馬苔状線維軸索興奮性の局所制御  [招待講演]

  神谷 温之

  第120回日本解剖学会総会･全国学術集会・第92回日本生理学会大会合同大会シンポジウム 2015年03月
• Fine control of axonal spikes by neural activity  [招待講演]

  Haruyuki Kamiya

  The 3rd RIEC International Symposium on Brain Functions and Brain Computer 2015年02月 シンポジウム・ワークショップパネル（指名）
• グルタミン酸受容体の時空間制御におけるシナプス後肥厚の役割  [招待講演]

  鈴木 江津子, 神谷 温之

  第91回日本生理学会大会シンポジウム 2014年03月
• Network mechanism of high frequency oscillation in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 2nd RIEC International Symposium on Brain Functions and Brain Computer 2014年02月 シンポジウム・ワークショップパネル（指名）
• AMPA受容体ダイナミクスの光化学的解析  [招待講演]

  神谷 温之

  第90回日本生理学会大会シンポジウム 2013年03月
• ケミカルニューロバイオロジー : 新たな分子ツールによる神経研究の新戦略 (S37)  [通常講演]

  神谷 温之, 尾藤 晴彦

  日本生理学雜誌 2013年03月
• Towards input-specific photoinactivation of neuronal networks in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 1st RIEC International Symposium on Brain Functions and Brain Computer 2012年11月 シンポジウム・ワークショップパネル（指名）
• 光反応性ブロッカーを用いたグルタミン酸受容体動態のシナプス「その場」解析  [招待講演]

  神谷 温之

  第89回日本生理学会大会シンポジウム 2012年03月
• シナプス前リアノジン受容体による海馬苔状線維シナプス可塑性の増幅機構  [通常講演]

  神谷温之

  日本生理学雑誌 2007年11月
• シナプス前リアノジン受容体による海馬苔状線維シナプス可塑性の増幅機構  [招待講演]

  神谷温之

  第30回日本神経科学学会大会 2007年09月 シンポジウム・ワークショップパネル（公募）
• カルシウムストアと海馬プレシナプス可塑性  [招待講演]

  神谷 温之

  第30回日本神経科学学会大会シンポジウム 2007年09月
• グルタミン酸・GABA共放出仮説の再検討  [通常講演]

  神谷温之

  日本生理学雑誌 2007年06月
• 海馬苔状線維シナプスにおけるGABA放出仮説の再検討  [通常講演]

  神谷 温之

  日本生理学会大会発表要旨集 2006年 

  It has been hypothesized that hippocampal mossy fiber terminals of young rodents release GABA in addition to glutamate. Using whole cell-clamp recordings in mouse slice preparations, I re-examined this possibility with paying attentions about the conditions to evoke monosynaptic GABAergic responses by stimulation of mossy fibers. Strong stimulus to the stratum granulosum of dentate gyrus or stimulus to the stratum lucidum of CA3 region elicited IPSCs in CA3 neurons in the presence of glutamate receptor antagonists 10 μM CNQX and 25 μM D-AP5, and these putative "monosynaptic IPSCs" were abolished by addition of GABA_A receptor antagonist 100 μM picrotoxin. In contrast, weak stimulus to the stratum granulosum never elicited IPSCs in the presence of CNQX and D-AP5. The responses to weak and strong stimuli also displayed differential sensitivity to group II mGluR agonist DCG-IV; application of 1 μM DCG-IV almost abolished the responses to weak stimulus and left substantial responses to strong stimulus which were inhibited by further application of picrotoxin. These results suggested that strong stimulus to stratum granulosum causes monosynaptic IPSCs by stimulating inhibitory interneurons in addition to mossy fibers, and mossy fiber terminals themselves may not release GABA. [J Physiol Sci. 2006;56 Suppl:S85]
• Presynaptic mechanisms for synaptic plasticity in the hippocampus  [招待講演]

  Haruyuki Kamiya

  Multi-institutional International Symposium on "mei" シンポジウム・ワークショップパネル（指名）
• Rab3 GAPによるシナプス伝達と可塑性の制御  [通常講演]

  坂根亜由子, 真鍋進治, 石崎宏好, 岡本三紀, 吉田隆行, 三好淳, 神谷温之, 高井義美, 佐々木卓也

  日本分子生物学会年会講演要旨集 2005年11月
• 海馬におけるシナプス可塑性の分子機構：シナプス前終末イメージング法を用いた研究  [招待講演]

  神谷温之

  第11回行動薬理研究会 2005年08月 口頭発表（招待・特別）
• 海馬スライスを用いたシナプス機能の研究  [招待講演]

  神谷温之

  第1回革新脳科学COE国内シンポジウム 2005年02月 シンポジウム・ワークショップパネル（指名）
• 転写因子RX/raxの発現によるマウスES細胞の網膜亜集団への分化(Retinal fate specification of mouse embryonic stem cells by ectopic expression of Rx/rax,a homeobox gene)  [通常講演]

  渡辺 すみ子, 田畑 陽子, 大内 靖夫, 神谷 温之, 真鍋 俊也, 新井 賢一

  神経化学 2004年08月
• 軸索標識法によるシナプス前終末内カルシウム動態の解析  [招待講演]

  神谷温之

  第77回日本薬理学会年会シンポジウム 2004年03月 シンポジウム・ワークショップパネル（指名）
• カイニン酸受容体を介するシナプス伝達・可塑性調節  [通常講演]

  神谷 温之

  日本生理学会大会発表要旨集 2004年 

  Kainate receptors (KARs) are poorly understood subtype of ionotropic glutamate receptors distributing widely and heterogeneously in the central nervous system (CNS). Recent studies elucidated the roles of KARs in activity-dependent modulation of synaptic transmission at certain synapses in the CNS, including hippocampal mossy fiber synapses where KAR subunits are most abundantly expressed. An important notice of these studies is that these receptors localize not only on postsynaptic but also on presynaptic membrane, and these presynaptic KARs impart an 'presynaptic' associativity to mossy fiber long-term potentiation (MF-LTP), an unusual form of plasticity that is independent of NMDA receptor activation and is expressed presynaptically. Homosynaptic as well as heterosynaptic positive feedback regulation of transmitter release via presynaptic KARs provides a novel way of signaling at the central synapses. To examine the cellular mechanism of activity-dependent modulation by presynaptic KARs, we adopted optical methods to monitor presynaptic Ca²⁺ and voltage transients at the mossy fiber synapses. We revealed that activation of presynaptic KARs elicits prominent depolarization of the presynaptic terminals and causes use-dependent facilitation of presynaptic Ca²⁺ influx by an action potential. Thus, presynaptic KARs at the mossy fiber synapses amplify presynaptic Ca²⁺ rise during repeated stimuli, and thereby affect the threshold of induction of MF-LTP. [Jpn J Physiol 54 Suppl:S33 (2004)]
• シナプス前カイニン酸受容体を介する海馬苔状線維の後脱分極応答  [通常講演]

  神谷温之, 真鍋俊也

  日本生理学雑誌 2002年10月
• γ1サブユニット欠損マウスを用いたカイニン酸型グルタミン酸受容体の機能解析  [通常講演]

  明石肇, 柿崎利和, 阿部学, 夏目里恵, 神谷温之, 深谷昌弘, 渡辺雅彦, 崎村建司

  生化学 2002年08月
• 神経系特異的AP‐3B複合体・μ3B遺伝子欠損マウスの作成・解析  [通常講演]

  中津史, 岡田元宏, 神谷温之, 原田彰宏, 若林孝一, 笠置泰史, 湯浅茂樹, 斉藤隆, 大野博司

  日本神経科学大会プログラム・抄録集 2002年07月
• forskolinによるマウス海馬苔状線維の興奮性の増強  [通常講演]

  梅田和昌, 神谷温之, 清原寿一, 真鍋俊也

  日本生理学雑誌 2002年04月
• 海馬苔状線維終末カルシウム流入促通へのカイニン酸受容体の関与  [招待講演]

  神谷温之, 真鍋俊也

  第79回日本生理学会大会 2002年03月 シンポジウム・ワークショップパネル（指名）
• 海馬シナプス前終末におけるカルシウム流入の可塑的変化  [招待講演]

  神谷温之

  第78回日本生理学会大会 2001年03月 シンポジウム・ワークショップパネル（指名）
• 神経系特異的AP‐3B複合体・μ3B遺伝子欠損マウスの作成・解析  [通常講演]

  中津史, 湯浅茂樹, 岩佐博人, 神谷温之, 真鍋俊也, 斉藤隆, 大野博司

  日本細胞生物学会大会講演要旨集 2001年
• 海馬苔状線維終末におけるカルシウム流入の促通  [通常講演]

  神谷温之, 小沢瀞司

  日本神経科学大会プログラム・抄録集 2000年09月
• 海馬シナプス前終末の可塑性メカニズムに関する研究  [通常講演]

  神谷温之

  日本生理学雜誌 2000年04月
• Rab GDIα欠損マウスの表現型解析 Rab GDIαの神経伝達物質放出に対する抑制作用  [通常講演]

  石橋宏好, 三好淳, 戸川温, 田中三紀, 神谷温之, 小沢瀞司, 阪口岳, 佐々木卓也, 高井義美

  日本分子生物学会年会プログラム・講演要旨集 1999年11月
• Presynaptic glutamate receptors in the hippocampus  [招待講演]

  Haruyuki Kamiya

  The 75th Annual Meeting of the Physiological Society of Japan Satellite Symposium “Slow synaptic responses and modulation” シンポジウム・ワークショップパネル（指名）
• 甲殻類ニューロンと哺乳類中枢ニューロンのシナプス前終末内Ca2+動態と短期可塑性  [招待講演]

  神谷温之

  第74回日本生理学会大会シンポジウム 1997年03月 シンポジウム・ワークショップパネル（指名）
• Suppression of presynaptic calcium influx by metabotropic glutamate receptor agonists in neonatal rat hippocampus  [招待講演]

  Haruyuki Kamiya

  The 25th Seminar on Science and Technology―Neuroscience 公開講演，セミナー，チュートリアル，講習，講義等
• Long-term potentiation in the mossy fiber-CA3 synapse of the guinea pig  [招待講演]

  Haruyuki Kamiya

  The International Workshop on Plasticity of Synaptic Transmission シンポジウム・ワークショップパネル（指名）

その他活動・業績

• Activity-dependent broadening of axonal spikes by inactivating K channels

  Haruyuki Kamiya ModelDB #267617 2023年04月
• Axonal subthreshold voltage signaling along hippocampal mossy fiber

  Kamiya H ModelDB #267512 2022年08月 [査読無し][通常論文]
  
• Evaluation of passive component of propagating AP in mossy fiber axons

  Kamiya H ModelDB #263034 2020年06月 [査読無し][招待有り]
  
• グルタミン酸受容体の時空間制御におけるシナプス後肥厚の役割

  鈴木江津子, 神谷温之 日本生理学雑誌 76 (4 (Web)) WEB ONLY 2014年 [査読無し][通常論文]
  
• 海馬スライスにおける内在性AMPA受容体動態の光化学的不活化解析

  神谷 温之 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (4) 146 -146 2013年09月01日
• カイニン酸型グルタミン酸受容体

  鈴木江津子, 神谷温之 脳科学辞典 2013年08月 [査読有り][招待有り]
  
• ケミカルニューロバイオロジー : 新たな分子ツールによる神経研究の新戦略 (S37)

  神谷 温之, 尾藤 晴彦 日本生理学雜誌 75 (2) 92 -96 2013年03月01日
• 海馬シナプスにおける神経活動依存的な伝達物質スイッチング

  神谷温之 脳の神経回路の機能解明 平成16-21年度 No.16069101 144 -145 2010年 [査読無し][通常論文]
  
• NMDA RECEPTOR GLUN2B SUBUNIT IS CRUCIAL FOR CHANNEL FUNCTION AND POST-SYNAPTIC MOLECULAR ORGANIZATION AT HIPPOCAMPAL CA3 SYNAPSES

  K. Sakimura, K. Akashi, T. Kakizaki, H. Kamiya, M. Fukaya, M. Yamasaki, M. Abe, R. Natsume, M. Watanabe JOURNAL OF NEUROCHEMISTRY 110 92 -92 2009年09月 [査読無し][通常論文]
  
• 神経可塑性のシナプス前性メカニズム

  神谷温之 金沢大学十全医学会雑誌 117 (3) 94 -95 2008年09月01日 [査読無し][通常論文]
   

  研究紹介2010年10月より全文公開.
• 神経回路研究に利用される技術 3.蛍光色素を用いたシナプス前部機能イメージング

  神谷温之 実験医学 26 (12) 1979 -1984 2008年07月18日 [査読無し][通常論文]
  
• 【神経回路の制御と脳機能発現のメカニズム 細胞移動・接着から記憶・学習・行動発現までの分子基盤解明と研究を躍進させる最新技術】 神経回路研究に利用される技術 蛍光色素を用いたシナプス前部機能イメージング

  神谷 温之 実験医学 26 (12) 1979 -1984 2008年07月 [査読無し][通常論文]
   

  中枢神経系におけるシナプス前部の機能解析は、その微小性に由来するさまざまな技術的制約により、例外的に巨大でシナプス前部からのパッチクランプ記録が可能な脳幹の内側台形体核(MNTB)シナプスなどのいくつかのモデルシナプスに限られてきた。しかしながら、安全率の高い情報伝達に特化した脳幹シナプスの解析から得た結論を脳の他のシナプスに一般化できないのは自明である。本稿では、顕著な可塑性を示す海馬や小脳のシナプスでシナプス前部のCa2+動態や膜電位変化などの機能的情報を評価する方法について紹介する。(著者抄録)
• The role of TARP gamma-8 (DVCC gamma-8) in AMPA receptor localization and function in hippocampus

  M Tsujita, M Fukaya, H Kamiya, M Abe, M Yamazaki, E Kushiya, R Natsume, M Watanabe, K Sakimura JOURNAL OF PHARMACOLOGICAL SCIENCES 100 76P -76P 2006年 [査読無し][通常論文]
  
• Rab3 GAPによるシナプス伝達と可塑性の制御

  坂根亜由子, 真鍋進治, 石崎宏好, 岡本三紀, 吉田隆行, 三好淳, 神谷温之, 高井義美, 佐々木卓也 日本分子生物学会年会講演要旨集 28th 307 2005年11月25日 [査読無し][通常論文]
  
• NMDA receptor GLUR epsilon 2/NR2B subunit is crucial for hippocampal synaptic functions

  K Akashi, T Kakizaki, H Kamiya, M Fukaya, M Watanabe, K Sakimura JOURNAL OF NEUROCHEMISTRY 94 59 -59 2005年08月 [査読無し][通常論文]
  
• PROFILE

  神谷温之 日本生理学雜誌 = JOURNAL OF THE PHYSIOLOGICAL SOCIETY OF JAPAN 66 (6) 198 -199 2004年06月01日 [査読無し][通常論文]
  
• 神経系特異的AP-3B複合体・μ3B遺伝子欠損マウスに見られるてんかん様けいれん発症機構の解析

  中津 史, 岡田 元宏, 岩佐 博人, Zhu Gang, 笠置 泰史, 森 文秋, 神谷 温之, 原田 彰宏, 下山 一郎, 若林 孝一, 真鍋 俊也, 兼子 直, 湯浅 茂樹, 齊藤 隆, 大野 博司 てんかん研究 21 (1) 37 -37 2003年02月 [査読無し][通常論文]
  
• 中枢神経の可塑性 第5回 高次脳機能 学習・記憶と海馬シナプス伝達の可塑性

  神谷温之, 真鍋俊也 総合リハビリテーション 30 (10) 915 -919 2002年10月10日 [査読無し][通常論文]
  
• 講座 中枢神経の可塑性(5)高次脳機能--学習・記憶と海馬シナプス伝達の可塑性

  神谷温之, 真鍋俊也 総合リハビリテ-ション 30 (10) 915 -919 2002年10月 [査読無し][通常論文]
  
• 神経系特異的AP‐3B複合体・μ3B遺伝子欠損マウスの作成・解析

  中津史, 岡田元宏, 神谷温之, 原田彰宏, 若林孝一, 笠置泰史, 湯浅茂樹, 斉藤隆, 大野博司 日本神経科学大会プログラム・抄録集 25th 192 2002年07月07日 [査読無し][通常論文]
  
• 脳の可塑性を支える分子機構 (特集《神経情報処理》最前線--情報科学と神経科学の融合)

  神谷温之 Computer today 19 (4) 24 -28 2002年07月 [査読無し][通常論文]
  
• 《神経情報処理》最前線 情報科学と神経科学の融合 脳の可塑性を支える分子機構

  神谷温之 Comput Today 19 (4) 24 -28 2002年07月01日 [査読無し][通常論文]
  
• forskolinによるマウス海馬苔状線維の興奮性の増強

  梅田和昌, 神谷温之, 清原寿一, 真鍋俊也 日本生理学雑誌 64 (4) 2002年
• シナプス前カイニン酸受容体を介する海馬苔状線維の後脱分極応答

  神谷温之, 真鍋俊也 日本生理学雑誌 64 (10) 2002年
• 脳研究の総合的推進に関する研究 神経終末活動の可視化によるシナプス可塑性メカニズムの解明

  神谷温之 脳研究の総合的推進に関する研究 平成12年度採択公募班員 11 2002年 [査読無し][通常論文]
  
• Establishment of neuron-specific mu 3B-deficient mice

  F Nakatsu, S Yuasa, H Iwasa, H Kamiya, A Harada, T Manabe, T Saito, H Ohno MOLECULAR BIOLOGY OF THE CELL 12 377A -377A 2001年11月 [査読無し][通常論文]
  
• 海馬シナプス伝達可塑性の分子機構

  神谷温之, 真鍋俊也 遺伝子医学 5 (3) 499 -501 2001年08月10日 [査読無し][通常論文]
  
• 神経系特異的AP-3B複合体・μ3B遺伝子欠損マウスの作成・解析

  中津史, 湯浅茂樹, 岩佐博人, 神谷温之, 真鍋俊也, 斉藤隆, 大野博司 日本細胞生物学会大会講演要旨集 54th 2001年
• 海馬シナプス前終末の可塑性メカニズムに関する研究

  神谷 温之 日本生理学雜誌 62 (4) 134 -135 2000年04月01日
• シナプス可塑性の新しい解析法 神経終末内カルシウム測定を用いたアプローチ

  神谷温之 生理学研究所年報 20 447 -448 1999年12月01日 [査読無し][通常論文]
  
• Rab GDIα欠損マウスの表現型解析 Rab GDIαの神経伝達物質放出に対する抑制作用

  石橋宏好, 三好淳, 戸川温, 田中三紀, 神谷温之, 小沢瀞司, 阪口岳, 佐々木卓也, 高井義美 日本分子生物学会年会プログラム・講演要旨集 22nd 475 1999年11月22日 [査読無し][通常論文]
  
• 海馬苔状線維終末に発現するシナプス前カイニン酸型グルタミン酸受容体の機能 (文部省S)

  神谷温之 神経回路の機能発達4 平成11年 117 -118 1999年 [査読無し][通常論文]
  
• シナプス前グルタミン酸受容体による中枢シナプス伝達制御機構の解析

  神谷温之 日産科学振興財団研究報告書 21 (21) 175 -178 1998年12月 [査読無し][通常論文]
  
• Glutamate receptors in the mammalian central nervous system

  S Ozawa, H Kamiya, K Tsuzuki PROGRESS IN NEUROBIOLOGY 54 (5) 581 -618 1998年04月 [査読有り][通常論文]
   

  Glutamate receptors (GluRs) mediate most of the excitatory neurotransmission in the mammalian central nervous system (CNS). In addition, they are involved in plastic changes in synaptic trans mission as well as excitotoxic neuronal cell death that occurs in a variety of acute and chronic neurological disorders. The GluRs are divided into two distinct groups, ionotropic and metabotropic receptors. The ionotropic receptors (iGluRs) are further subdivided into three groups: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (MMDA) receptor channels. The metabotropic receptors (mGluRs) are coupled to GTP-binding proteins (G-proteins), and regulate the production of intracellular messengers. The application of molecular cloning technology has greatly advanced our understanding of the GluR system. To date, at least 14 cDNAs of subunit proteins constituting iGluRs and 8 cDNAs of proteins coznstituting mGluRs have been cloned in the mammalian CNS, and the molecular structure, distribution and developmental change in the CNS, Functional and pharmacological properties of each receptor subunit have been elucidated. Furthermore, the obtained clones have provided valuable tools for conducting studies to clarify the physiological and pathophysiological significances of each subunit. For example, the generation of gene knockout mice has disclosed critical roles of some GluR subunits in brain functions. In this article, we review recent progress in the research for GluRs with special emphasis on the molecular diversity of the GluR system and its implications for physiology and pathology of the CNS. (C) 1998 Elsevier Science Ltd.
• シナプス前カイニン酸型グルタミン酸受容体による海馬苔状線維シナプス伝達の強化 (文部省S)

  神谷温之 神経回路の機能発達3 平成10年 103 -104 1998年 [査読無し][通常論文]
  
• シナプス可塑性の物質的基盤 Caイオンと可塑性

  神谷温之 Clin Neurosci 15 (10) 1108 -1110 1997年10月 [査読無し][通常論文]
  
• 海馬単一神経終末イメージングによる中枢シナプス強化機構の研究 (文部省S)

  神谷温之 神経回路の機能発達2 平成9年 113 -114 1997年 [査読無し][通常論文]
  
• 長期増強の起源

  山本 長三郎, 神谷 温之 日本生理学雑誌 57 (増刊) 217 -223 1995年03月 [査読無し][通常論文]
  
• 海馬における長期増強

  山本長三郎, 神谷温之 神経研究の進歩 35 (6) 926 -932 1991年12月 [査読無し][通常論文]
  
• 特集 記憶の分子メカニズム 長期増強を中心に 記憶と長期増強

  神谷温之, 山本長三郎 実験医学 8 (12) 1553 -1559 1990年08月 [査読無し][招待有り]
  

受賞

• 1999年 日本生理学会 奨励賞
   

  受賞者: 神谷 温之

共同研究・競争的資金等の研究課題

• 軸索における異所性スパイク発生機構のサブセルラー解析

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2021年04月 -2024年03月 

  代表者 : 神谷 温之
• 軸索による高速ネットワーク律動の発振メカニズムの解明

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2018年 -2020年 

  代表者 : 神谷 温之
• 軸索のサブセルラー機能解析システムと最適化モデルの構築

  文部科学省：科学研究費補助金（挑戦的萌芽研究）

  研究期間 : 2016年 -2018年 

  代表者 : 神谷 温之
• 術後認知機能障害の機序ー神経炎症からの検討ー

  文部科学省：科学研究費補助金（基盤研究(C) ）

  研究期間 : 2013年 -2016年 

  代表者 : 森本 裕二
• 単一神経終末エレクトロポレーションによるシナプス前ギャップ結合の機能解析

  文部科学省：科学研究費補助金（挑戦的萌芽研究）

  研究期間 : 2013年 -2015年 

  代表者 : 神谷 温之
• グルタミン酸受容体トラフィックにおけるシナプス後肥厚の動的役割

  文部科学省：科学研究費補助金(基盤研究(B))

  研究期間 : 2012年 -2014年 

  代表者 : 神谷温之
• 光学的シナプス不活化法による脳内局所神経回路の機能探索

  文部科学省：科学研究費補助金(挑戦的萌芽研究)

  研究期間 : 2011年 -2012年 

  代表者 : 神谷温之
• 海馬シナプス前カルシウムストアの細胞分子基盤に関する研究

  文部科学省：科学研究費補助金(基盤研究(B))

  研究期間 : 2009年 -2011年 

  代表者 : 神谷温之
• シナプス前クロライド濃度勾配の発生機構の解明

  文部科学省：科学研究費補助金(挑戦的萌芽研究)

  研究期間 : 2009年 -2010年 

  代表者 : 神谷温之
• 光分子不活化法によるシナブス機能の光操作法の開発

  文部科学省：科学研究費補助金(萌芽研究)

  研究期間 : 2006年 -2007年
• 光不活化法によるグルタミン酸受容体トラフィックのリアルタイム解析

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2006年 -2007年
• 海馬シナプスにおける神経活動依存的な伝達物質スイッチング

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2006年 -2007年
• 海馬苔状線維シナプスにおけるグルタミン酸・GABA共放出仮説の検討

  文部科学省：科学研究費補助金(基盤研究(B))

  研究期間 : 2005年 -2007年
• 海馬シナプスにおけるグルタミン酸・GABA共放出のメカニズム

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2005年 -2005年
• 海馬シナプス前終末に発現するイオンチャンネル型ATP受容体の作用機構

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2004年 -2005年
• シナプス前カイニン酸受容体による海馬苔状線維終末内カルシウム動態の増幅機構

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2004年 -2004年
• 海馬苔状線維シナプスにおける神経終末内カルシウムストアの機能

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2003年 -2004年
• シナプス前終末内カルシウムストアによる中枢シナプス可塑性の調節機構

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2003年 -2004年
• シナプス前カイニン酸受容体による海馬苔状線維シナプス可塑性の制御機構

  文部科学省：科学研究費補助金(特定領域研究)

  研究期間 : 2003年 -2003年
• 海馬苔状線維終末におけるカルシウム動態の可塑性メカニズム

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2001年 -2002年
• 神経終末パッチクランプ法による海馬苔状線維シナプス可塑性メカニズムの解析

  文部科学省：科学研究費補助金(特定領域研究(A), 特定領域研究)

  研究期間 : 2001年 -2002年
• 神経終末活動の可視化によるシナプス可塑性メカニズムの解明

  文部科学省：科学研究費補助金(特定領域研究(A))

  研究期間 : 2000年 -2001年
• 光学的測定による海馬苔状線維シナプス長期増強の誘発・発現機構の解析

  文部科学省：科学研究費補助金(特定領域研究(A))

  研究期間 : 2000年 -2000年
• 神経終末内カルシウムと開口放出の同時測定による海馬苔状線維シナプス可塑性の解析

  文部科学省：科学研究費補助金(奨励研究(A))

  研究期間 : 1999年 -2000年
• シナプス前終末ミトコンドリア内カルシウム動態の可視化とシナプス可塑性

  文部科学省：科学研究費補助金(特定領域研究(A))

  研究期間 : 1998年 -1998年
• 海馬苔状線維終末に発現するシナプス前カイニン酸型グルタミン酸受容体の機能

  文部科学省：科学研究費補助金(特定領域研究(A))

  研究期間 : 1998年 -1998年
• 海馬苔状線維終末に発現するシナプス前カイニン酸型グルタミン酸受容体の機能

  文部科学省：科学研究費補助金(奨励研究(A))

  研究期間 : 1997年 -1998年
• シナプス前カイニン酸型グルタミン酸受容体による海馬苔状線維シナプス伝達の強化

  文部科学省：科学研究費補助金(重点領域研究)

  研究期間 : 1997年 -1997年
• 海馬単一神経終末イメ-ジングによるシナプス前カルシウム・ストアの研究

  文部科学省：科学研究費補助金(奨励研究(A))

  研究期間 : 1996年 -1996年
• 海馬単一神経終末イメ-ジングによる中枢シナプス強化機構の研究

  文部科学省：科学研究費補助金(重点領域研究)

  研究期間 : 1996年 -1996年
• 神経終末内カルシウム貯蔵部位によるシナブス可塑性の調節

  文部科学省：科学研究費補助金(奨励研究(A))

  研究期間 : 1995年 -1995年
• 細胞内カルシウム放出機構による中枢シナプス可塑性の調節

  文部科学省：科学研究費補助金(重点領域研究)

  研究期間 : 1995年 -1995年
• 中枢シナプスにおける伝達物質放出の修飾機構ー素量解析による研究

  文部科学省：科学研究費補助金(一般研究(B))

  研究期間 : 1989年 -1991年
• シナプス前膜カルシウムチャンネルとシナプス可塑性-パッチクランプ法による研究

  文部科学省：科学研究費補助金(重点領域研究)

  研究期間 : 1989年 -1989年

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