2021/10/30 更新

写真a

イノウエ ツヨシ
井上 剛
INOUE Tsuyoshi
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 博士(薬学) ( 東京大学 )

研究キーワード

  • てんかん

  • ケトン食

  • 電気生理学

  • 創薬開発

研究分野

  • ライフサイエンス / 生物物理学

  • ライフサイエンス / 薬系分析、物理化学

  • ライフサイエンス / 病態神経科学

学歴

  • 東京大学   大学院薬学系研究科  

    1996年 - 2001年

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    国名: 日本国

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  • 東京大学   薬学部  

    1992年 - 1996年

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    国名: 日本国

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経歴

  • 岡山大学   大学院医歯薬学総合研究科   准教授

    2008年 - 現在

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  • 生理学研究所   助教

    2007年 - 2008年

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  • 生理学研究所   助手

    2003年 - 2007年

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  • ケースウェスタンリザーブ大学   博士研究員

    2001年 - 2003年

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論文

  • Upregulation of lactate dehydrogenase A in a chronic model of temporal lobe epilepsy 査読

    Nagisa Sada, Shogo Suto, Mana Suzuki, Shoichiro Usui, Tsuyoshi Inoue

    Epilepsia   61 ( 5 )   2020年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/epi.16488

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/epi.16488

  • Electrical Control in Neurons by the Ketogenic Diet 査読

    Nagisa Sada, Tsuyoshi Inoue

    Frontiers in Cellular Neuroscience   12   2018年7月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    DOI: 10.3389/fncel.2018.00208

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  • Structure–activity relationship of porphyrin-induced photoinactivation with membrane function in bacteria and erythrocytes 査読

    Hisato Kato, Keiko Komagoe, Tsuyoshi Inoue, Kazufumi Masuda, Takashi Katsu

    Photochemical & Photobiological Sciences   17 ( 7 )   954 - 963   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry (RSC)  

    <p>We analyzed the structure–activity relationship of natural porphyrins and the related analogs with the photoinactivation of membrane function in bacteria and erythrocytes.</p>

    DOI: 10.1039/c8pp00092a

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  • Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain 査読

    Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji

    Proceedings of the National Academy of Sciences   114 ( 31 )   E6297 - E6305   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Proceedings of the National Academy of Sciences  

    Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission. In vitro analyses indicated that clodronate inhibits VNUT at a half-maximal inhibitory concentration of 15.6 nM without affecting other vesicular neurotransmitter transporters, acting as an allosteric modulator through competition with Cl<sup>−</sup>. A low concentration of clodronate impaired vesicular ATP release from neurons, microglia, and immune cells. In vivo analyses revealed that clodronate is more effective than other therapeutic agents in attenuating neuropathic and inflammatory pain, as well as the accompanying inflammation, in wild-type but not <italic>VNUT</italic><sup>−/−</sup> mice, without affecting basal nociception. These findings indicate that clodronate may represent a unique treatment strategy for chronic neuropathic and inflammatory pain via inhibition of vesicular ATP release.

    DOI: 10.1073/pnas.1704847114

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  • Neuronal inhibition and seizure suppression by acetoacetate and its analog, 2‐phenylbutyrate 査読

    Atsushi Kadowaki, Nagisa Sada, Narinobu Juge, Ayaka Wakasa, Yoshinori Moriyama, Tsuyoshi Inoue

    Epilepsia   58 ( 5 )   845 - 857   2017年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/epi.13718

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/epi.13718

  • Synaptic Multivesicular Release in the Cerebellar Cortex: Its Mechanism and Role in Neural Encoding and Processing 査読

    Shin’Ichiro Satake, Tsuyoshi Inoue, Keiji Imoto

    The Cerebellum   15 ( 2 )   201 - 207   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s12311-015-0677-5

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    その他リンク: http://link.springer.com/article/10.1007/s12311-015-0677-5/fulltext.html

  • Targeting LDH enzymes with a stiripentol analog to treat epilepsy 査読

    N. Sada, S. Lee, T. Katsu, T. Otsuki, T. Inoue

    Science   347 ( 6228 )   1362 - 1367   2015年3月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Association for the Advancement of Science (AAAS)  

    DOI: 10.1126/science.aaa1299

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  • Synthesis of antimicrobial cyclodextrins bearing polyarylamino and polyalkylamino groups via click chemistry for bacterial membrane disruption 査読

    Hatsuo Yamamura, Yuuki Sugiyama, Kensuke Murata, Takanori Yokoi, Ryuji Kurata, Atsushi Miyagawa, Kenji Sakamoto, Keiko Komagoe, Tsuyoshi Inoue, Takashi Katsu

    Chemical Communications   50 ( 41 )   5444 - 5444   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry (RSC)  

    DOI: 10.1039/c3cc49543d

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  • In situ potentiometric method to evaluate bacterial outer membrane-permeabilizing ability of drugs: Example using antiprotozoal diamidines 査読

    Makoto Ando, Rie Kamei, Keiko Komagoe, Tsuyoshi Inoue, Keiichi Yamada, Takashi Katsu

    Journal of Microbiological Methods   91 ( 3 )   497 - 500   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.mimet.2012.09.033

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  • Paired-pulse facilitation of multivesicular release and intersynaptic spillover of glutamate at rat cerebellar granule cell-interneurone synapses 査読

    Shin’Ichiro Satake, Tsuyoshi Inoue, Keiji Imoto

    The Journal of Physiology   590 ( 22 )   5653 - 5675   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1113/jphysiol.2012.234070

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  • Xanthene Dyes Induce Membrane Permeabilization of Bacteria and Erythrocytes by Photoinactivation 査読

    Hisato Kato, Keiko Komagoe, Yuka Nakanishi, Tsuyoshi Inoue, Takashi Katsu

    Photochemistry and Photobiology   88 ( 2 )   423 - 431   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/j.1751-1097.2012.01080.x

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  • Roles of the subthalamic nucleus and subthalamic HCN channels in absence seizures 査読

    Daisuke Kase, Tsuyoshi Inoue, Keiji Imoto

    Journal of Neurophysiology   107 ( 1 )   393 - 406   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    Absence seizures consist of a brief and sudden impairment of consciousness. They are characterized by bilaterally synchronized spike and wave discharges (SWDs), which reflect abnormal oscillations in the thalamocortical loops. Recent studies have suggested that the basal ganglia are involved in generation of the SWDs, but their roles are poorly understood at the molecular and cellular levels. Here we studied the pathophysiological roles of the basal ganglia, using in vivo and in vitro measurements of tottering mice, a well-established model of absence epilepsy. We found that the membrane excitability in subthalamic nucleus (STN) neurons was enhanced in tottering mice, which resulted from reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. Pharmacological blockade and activation of HCN channel activity in vitro bidirectionally altered the membrane excitability of the STN neurons. Furthermore, these pharmacological modulations of HCN channel activity in the STN in vivo bidirectionally altered the mean SWD duration. In addition, STN deep brain stimulation modulated SWDs in a frequency-dependent manner. These results indicate that STN is involved in the rhythm maintenance system of absence seizures.

    DOI: 10.1152/jn.00937.2010

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  • Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Abeta generation in Alzheimer's disease 査読

    Yuhki Saito, Tsuyoshi Inoue, Gang Zhu, Naoki Kimura, Motohiro Okada, Masaki Nishimura, Nobuyuki Kimura, Shigeo Murayama, Sunao Kaneko, Ryuichi Shigemoto, Keiji Imoto, Toshiharu Suzuki

    Molecular Neurodegeneration   7 ( 1 )   50 - 50   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1186/1750-1326-7-50

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  • Comparative study of the membrane-permeabilizing activities of mastoparans and related histamine-releasing agents in bacteria, erythrocytes, and mast cells 査読

    Satoshi Nakao, Keiko Komagoe, Tsuyoshi Inoue, Takashi Katsu

    Biochimica et Biophysica Acta (BBA) - Biomembranes   1808 ( 1 )   490 - 497   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbamem.2010.10.007

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  • Continuous real-time monitoring of cationic porphyrin-induced photodynamic inactivation of bacterial membrane functions using electrochemical sensors 査読

    Keiko Komagoe, Hisato Kato, Tsuyoshi Inoue, Takashi Katsu

    Photochemical & Photobiological Sciences   10 ( 7 )   1181 - 1181   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry (RSC)  

    DOI: 10.1039/c0pp00376j

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  • Metabolic Control of Vesicular Glutamate Transport and Release 査読

    Narinobu Juge, John A. Gray, Hiroshi Omote, Takaaki Miyaji, Tsuyoshi Inoue, Chiaki Hara, Hisayuki Uneyama, Robert H. Edwards, Roger A. Nicoll, Yoshinori Moriyama

    Neuron   68 ( 1 )   99 - 112   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.neuron.2010.09.002

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  • Application of an Oxygen Electrode to Evaluate Superoxide Anion-scavenging Ability 査読

    Keiko KOMAGOE, Hiroaki TAKEUCHI, Tsuyoshi INOUE, Takashi KATSU

    Analytical Sciences   26 ( 8 )   903 - 906   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Society for Analytical Chemistry  

    DOI: 10.2116/analsci.26.903

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  • In Situ Monitoring of Photodynamic Inactivation of the Membrane Functions of Bacteria Using Electrochemical Sensors 査読

    Hisato KATO, Keiko KOMAGOE, Tsuyoshi INOUE, Takashi KATSU

    Analytical Sciences   26 ( 10 )   1019 - 1021   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Society for Analytical Chemistry  

    DOI: 10.2116/analsci.26.1019

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  • Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System 査読 国際誌

    Tetsuya Shiuchi, Mohammad Shahidul Haque, Shiki Okamoto, Tsuyoshi Inoue, Haruaki Kageyama, Suni Lee, Chitoku Toda, Atsushi Suzuki, Eric S. Bachman, Young-Bum Kim, Takashi Sakurai, Masashi Yanagisawa, Seiji Shioda, Keiji Imoto, Yasuhiko Minokoshi

    Cell Metabolism   10 ( 6 )   466 - 480   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by activating the sympathetic nervous system. These effects of orexin were blunted in mice lacking beta-adrenergic receptors but were restored by forced expression of the beta(2)-adrenergic receptor in both myocytes and nonmyocyte cells of skeletal muscle. Orexin neurons are activated by conditioned sweet tasting and directly excite VMH neurons, thereby increasing muscle glucose metabolism and its insulin sensitivity. Orexin and its receptor in VMH thus play a key role in the regulation of muscle glucose metabolism associated with highly motivated behavior by activating muscle sympathetic nerves and beta(2)-adrenergic signaling.

    DOI: 10.1016/j.cmet.2009.09.013

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  • Transient Activity Induces a Long-Lasting Increase in the Excitability of Olfactory Bulb Interneurons 査読

    Tsuyoshi Inoue, Ben W. Strowbridge

    Journal of Neurophysiology   99 ( 1 )   187 - 199   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    Little is known about the cellular mechanisms that underlie the processing and storage of sensory in the mammalian olfactory system. Here we show that persistent spiking, an activity pattern associated with working memory in other brain regions, can be evoked in the olfactory bulb by stimuli that mimic physiological patterns of synaptic input. We find that brief discharges trigger persistent activity in individual interneurons that receive slow, subthreshold oscillatory input in acute rat olfactory bulb slices. A 2- to 5-Hz oscillatory input, which resembles the synaptic drive that the olfactory bulb receives during sniffing, is required to maintain persistent firing. Persistent activity depends on muscarinic receptor activation and results from interactions between calcium-dependent afterdepolarizations and low-threshold Ca spikes in granule cells. Computer simulations suggest that intrinsically generated persistent activity in granule cells can evoke correlated spiking in reciprocally connected mitral cells. The interaction between the intrinsic currents present in reciprocally connected olfactory bulb neurons constitutes a novel mechanism for synchronized firing in subpopulations of neurons during olfactory processing.

    DOI: 10.1152/jn.00526.2007

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  • Precise Size Determination of Amphotericin B and Nystatin Channels Formed in Erythrocyte and Liposomal Membranes Based on Osmotic Protection Experiments 査読

    Takashi KATSU, Shiho OKADA, Tomonori IMAMURA, Keiko KOMAGOE, Kazufumi MASUDA, Tsuyoshi INOUE, Satoshi NAKAO

    Analytical Sciences   24 ( 12 )   1551 - 1556   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Society for Analytical Chemistry  

    DOI: 10.2116/analsci.24.1551

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  • Muscarinic Receptor Activation Modulates Granule Cell Excitability and Potentiates Inhibition onto Mitral Cells in the Rat Olfactory Bulb 査読

    R. T. Pressler, T. Inoue, B. W. Strowbridge

    Journal of Neuroscience   27 ( 41 )   10969 - 10981   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Society for Neuroscience  

    DOI: 10.1523/jneurosci.2961-07.2007

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  • Feedforward Inhibitory Connections From Multiple Thalamic Cells to Multiple Regular-Spiking Cells in Layer 4 of the Somatosensory Cortex 査読

    Tsuyoshi Inoue, Keiji Imoto

    Journal of Neurophysiology   96 ( 4 )   1746 - 1754   2006年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    Thalamocortical (TC) cells in the ventrobasal thalamus make direct excitatory connections with regular-spiking (RS) cells in layer 4 of the somatosensory cortex, but also make disynaptic feedforward inhibitory connections with the RS cells by layer 4 fast-spiking (FS) cells. In this study, we investigated connection rules of the feedforward inhibitory circuit from multiple TC cells to multiple RS cells, at the level of synaptic potentials. Using thalamocortical brain slices of young mice (postnatal days 12–16), we made simultaneous patch-clamp recordings from three adjacent cortical cells (two RS cells and one FS cell), combined with minimal stimulation of presumed single TC fibers. We found that nearly all (97%) of TC fibers, which generated excitatory inputs onto RS cells, also generated divergent excitatory inputs onto adjacent FS cells. Some 44% of TC fibers generated divergent excitatory inputs onto adjacent pairs of RS cells. We then combined the triple patch-clamp recording with multisite (two to three) minimal stimulation of single TC fibers and found that 86% of FS cells received convergent inputs from all of the stimulated TC fibers. We also found that 68% of FS cells generated divergent inhibitory inputs onto adjacent pairs of RS cells. The results indicate that spikes in TC cells, which excite RS cells, also excite adjacent FS cells with high fidelity. The results also indicate that FS cells receive convergent excitatory inputs from multiple TC cells and then send divergent inhibitory outputs to multiple RS cells.

    DOI: 10.1152/jn.00301.2006

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  • In Vitro Odor-Aversion Conditioning in a Terrestrial Mollusk 査読

    Tsuyoshi Inoue, Masayoshi Murakami, Satoshi Watanabe, Yasuko Inokuma, Yutaka Kirino

    Journal of Neurophysiology   95 ( 6 )   3898 - 3903   2006年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    We developed an in vitro odor-aversion conditioning system in the terrestrial mollusk, Limax, and found a behavioral correlate of network oscillation in the olfactory CNS. We first examined the odor-induced behavior of Limax, after odor-aversion conditioning in vivo. Shortening of mantle muscles was specifically observed in response to aversively conditioned odors. We previously identified that parietal nerves, which project to the mantle muscle in Limax, regulate shortening of the mantle muscle. We therefore isolated whole brains containing noses (sensory organs) and parietal nerves (motor output), and applied an odor-aversion conditioning paradigm to these in vitro preparations. Before the in vitro conditioning, application of attractive odors to the noses did not elicit any discharge in the parietal nerves. However, after odor-aversion conditioning, discharges in the parietal nerves were observed in response to the natively attractive but aversively conditioned odors. We also found that network oscillation frequency in the procerebrum (PC), the olfactory CNS of Limax, increased specifically in response to the aversively conditioned odors that elicited avoidance behavior. In naive (nonconditioned) preparations, increases in the PC oscillation frequency were observed specifically in response to innately aversive odors. These results indicate that the isolated brains have an ability of odor learning. They also suggest that changes in PC network oscillation are associated with aversively conditioned and innately aversive odors, both of which elicit avoidance behavior. This in vitro conditioning system would be an effective approach for exploring the neural mechanism to determine the aversion to odors.

    DOI: 10.1152/jn.00853.2005

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  • Impaired Feedforward Inhibition of the Thalamocortical Projection in Epileptic Ca2+ Channel Mutant Mice, tottering 査読 国際誌

    S. Sasaki, Kadrul Huda, Tsuyoshi Inoue, Mariko Miyata, Keiji Imoto

    Journal of Neuroscience   26 ( 11 )   3056 - 3065   2006年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Society for Neuroscience  

    The tottering (tg) mice have a mutation in the CaV2.1 (P/Q-type) voltage-dependent Ca2+ channel alpha(1)2.1 subunit gene. tg mice show not only cerebellar ataxia but also absence epilepsy, which begins at approximately 3 weeks of age and persists throughout life. Similarities in EEG and sensitivity to antiepileptic drugs suggest that tg mice are a good model for human absence epilepsy. Although imbalance between excitatory and inhibitory activity in the thalamocortical network is thought to contribute to the pathogenesis of absence epilepsy, the effect of the mutation on thalamocortical synaptic responses remains unknown. Here we showed imbalanced impairment of inhibitory synaptic responses in tg mice using brain slice preparations. Somatosensory thalamocortical projection makes not only monosynaptic glutamatergic connections but also disynaptic GABAergic connections, which mediate feedforward inhibition, onto layer IV neurons. In tg mice, IPSC amplitudes recorded from layer IV pyramidal cells of the somatosensory cortex in response to thalamic stimulation became disproportionately reduced compared with EPSC amplitudes at later developmental stages (postnatal days 21-30). Similar results were obtained by local stimulation of layer IV pyramidal neurons. However, IPSC reduction was not seen in layer V pyramidal neurons of epileptic tg mice or in layer IV pyramidal neurons of younger tg mice before the onset of epilepsy (postnatal days 14-16). These results showed that the feedforward inhibition from the thalamus to layer IV neurons of the somatosensory cortex was severely impaired in tg mice and that the impairment of the inhibitory synaptic transmission was correlated to the onset of absence epilepsy.

    DOI: 10.1523/jneurosci.5422-05.2006

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  • Odor-evoked responses in the olfactory center neurons in the terrestrial slug 査読

    Masayoshi Murakami, Satoshi Watanabe, Tsuyoshi Inoue, Yutaka Kirino

    Journal of Neurobiology   58 ( 3 )   369 - 378   2004年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/neu.10295

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  • In Vitro Study of Odor-Evoked Behavior in a Terrestrial Mollusk 査読

    Tsuyoshi Inoue, Yasuko Inokuma, Satoshi Watanabe, Yutaka Kirino

    Journal of Neurophysiology   91 ( 1 )   372 - 381   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    To explore neural mechanisms how olfactory information is processed in the brain and finally converted into behavior, it would be useful to have isolated whole brains that include both olfactory organs and motor output. In the present study, we identified an in vitro index of odor-evoked behavior in the terrestrial mollusk Limax and also studied the modulation of this in vitro index of the behavior. We determined that shortening of the mantle muscles is one of the withdrawal responses selectively induced by aversive odors and that the shortening is mediated by a pair of parietal nerves. We also identified a motoneuron (named the posterior visceral neuron, p-VN) that projects to the parietal nerve and innervates the mantle muscles. When we applied various odors to the nose in these isolated molluscan brains, only aversive odors induced discharges in the p-VN. These results indicate that p-VN discharges can serve as an in vitro index of odor-induced aversive behavior. We also identified a novel serotonergic neuron (named the posterior cerebral serotonergic cell, p-CSC). Discharges in the p-CSC released serotonin to the tentacle ganglion (TG); serotonin in the TG then inhibited odor-induced discharges in the p-VN, the in vitro index of aversive behavior. These results suggest that the serotonergic system is involved in the regulation of approach and avoidance behavior in Limax.

    DOI: 10.1152/jn.00247.2003

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  • Contribution of Excitatory Chloride Conductance in the Determination of the Direction of Traveling Waves in an Olfactory Center 査読

    Satoshi Watanabe, Tsuyoshi Inoue, Yutaka Kirino

    The Journal of Neuroscience   23 ( 7 )   2932 - 2938   2003年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Society for Neuroscience  

    DOI: 10.1523/jneurosci.23-07-02932.2003

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  • Two Types of Network Oscillations and Their Odor Responses in the Primary Olfactory Center of a Terrestrial Mollusk 査読

    Yasuko Inokuma, Tsuyoshi Inoue, Satoshi Watanabe, Yutaka Kirino

    Journal of Neurophysiology   87 ( 6 )   3160 - 3164   2002年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    We identified two classes of network oscillations with different frequency ranges in the tentacle ganglion (TG), the primary olfactory center of the terrestrial mollusk Limax marginatus, and investigated the responses of these oscillations to odor inputs. A recent study indicated that there are serotonergic terminals in the TG. We found that when serotonin was applied to the TG, the spontaneous network oscillation of about 1.5 Hz in the TG changed its oscillatory frequency to 0.5 Hz. These two oscillations are distinct, because 1) in most cases, the application of serotonin to the TG initially inhibited the 1.5-Hz oscillation and subsequently generated the slow 0.5-Hz oscillation; and 2) occasionally, the application of serotonin did not inhibit the spontaneous 1.5-Hz oscillation, resulting in the coexistence of two network oscillations. Thus the TG has two different oscillatory dynamics. We named the spontaneous 1.5-Hz oscillation the fast oscillation (FO), and the serotonin-induced 0.5-Hz oscillation the slow oscillation (SO). By calculating the spatial coherence of the TG oscillations, we found that the FO is a noncoherent oscillatory mode and the SO is a coherent oscillatory mode. Finally, odor presentation to the olfactory receptors selectively modulated the SO by decreasing the oscillatory amplitude, but the FO was not modulated by the odor input. These results indicate that 1) the TG has two oscillatory states (FO and SO) and these states are changed by the extracellular level of serotonin, and 2) these two oscillatory states have different responses to odors.

    DOI: 10.1152/jn.2002.87.6.3160

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  • Identification and characterization of an output neuron from the oscillatory molluscan olfactory network 査読

    Satoshi Shimozono, Satoshi Watanabe, Tsuyoshi Inoue, Yutaka Kirino

    Brain Research   921 ( 1-2 )   98 - 105   2001年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0006-8993(01)03096-7

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  • Serotonin and NO Complementarily Regulate Generation of Oscillatory Activity in the Olfactory CNS of a Terrestrial Mollusk 査読

    Tsuyoshi Inoue, Satoshi Watanabe, Yutaka Kirino

    Journal of Neurophysiology   85 ( 6 )   2634 - 2638   2001年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    Synchronous oscillation of membrane potentials, generated by assemblies of neurons, is a prominent feature in the olfactory systems of many vertebrate and invertebrate species. However, its generation mechanism is still controversial. Biogenic amines play important roles for mammalian olfactory learning and are also implicated in molluscan olfactory learning. Here, we investigated the role of serotonin, a biogenic amine, in the oscillatory dynamics in the procerebrum (PC), the molluscan olfactory center. Serotonin receptor blockers inhibited the spontaneous synchronous oscillatory activity of low frequency (approximately 0.5 Hz) in the PC. This was due to diminishing the periodic slow oscillation of membrane potential in bursting (B) neurons, which are essential neuronal elements for the synchronous oscillation in the PC. On the other hand, serotonin enhanced the amplitude of the slow oscillation in B neurons and subsequently increased the number of spikes in each oscillatory cycle. These results show that the extracellular serotonin level regulates the oscillation amplitude in B neurons and thus serotonin may be called an oscillation generator in the PC. Although nitric oxide (NO) is known to also be a crucial factor for generating the PC oscillatory activity and setting the PC oscillation frequency, the present study showed that NO only regulates the oscillation frequency in B neurons but could not increase the spikes in each oscillatory cycle. These results suggest complementary regulation of the PC oscillatory activity: NO determines the probability of occurrence of slow potentials in B neurons, whereas serotonin regulates the amplitude in each cycle of the oscillatory activity in B neurons.

    DOI: 10.1152/jn.2001.85.6.2634

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  • Modulation of oscillatory neural activities by cholinergic activation of interneurons in the olfactory center of a terrestrial slug 査読

    Satoshi Watanabe, Tsuyoshi Inoue, Masayoshi Murakami, Yasuko Inokuma, Shigenori Kawahara, Yutaka Kirino

    Brain Research   896 ( 1-2 )   30 - 35   2001年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0006-8993(00)03242-x

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  • Phase-Dependent Filtering of Sensory Information in the Oscillatory Olfactory Center of a Terrestrial Mollusk 査読

    Tsuyoshi Inoue, Satoshi Watanabe, Shigenori Kawahara, Yutaka Kirino

    Journal of Neurophysiology   84 ( 2 )   1112 - 1115   2000年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physiological Society  

    With electrophysiological techniques, we found phase-dependent modification of the efficacy of signal transmission in the procerebrum (PC), the oscillatory olfactory center, of the terrestrial mollusk Limax marginatus and elucidated its neuronal mechanism. Previous studies have indicated that about 10<sup>5</sup> PC neurons can be classified into only two types: bursting (B) neurons and nonbursting (NB) neurons, and both types of neurons have ongoing and phase-locked periodic oscillation of their membrane potentials. On olfactory nerve stimulation, excitatory postsynaptic potentials (EPSPs) were evoked with a constant latency in NB neurons, while EPSPs with a variable latency were evoked in B neurons. These findings suggest a monosynaptic connection from the olfactory nerve to NB neurons, but a polysynaptic connection between the olfactory nerve and B neurons. This polysynaptic transmission is most likely mediated by NB neurons because the olfactory nerve makes synaptic connection only with NB neurons in the PC. The latency of the evoked EPSPs in B neurons depended on the phase of the PC oscillatory activity, presumably because of the oscillation of the intervening NB neurons. These results suggest that the efficacy of olfactory nerve–B neuron polysynaptic transmission is regulated by the activity level of the phasically oscillating NB neurons. Thus, the intrinsic oscillation in the PC can serve as a filter for olfactory information conveyed from the olfactory nerve as a train of neuronal spikes. This filtering system may also produce a phase-dependent modification by the olfactory input of the PC oscillation frequency.

    DOI: 10.1152/jn.2000.84.2.1112

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MISC

  • グリアを狙うてんかん創薬 招待

    井上 剛, 佐田 渚

    実験医学   37 ( 17 )   2931 - 2937   2019年

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  • 乳酸脱水素酵素を標的とした難治性てんかん治療創製に関する研究 招待

    井上 剛, 佐田 渚

    感染・炎症・免疫   47 ( 1 )   79 - 81   2017年

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    記述言語:日本語  

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  • ケトン食・ケトン体による神経保護作用 招待

    井上 剛, 佐田 渚

    PRACTICE   34 ( 1 )   36 - 40   2017年

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  • 電気生理学が切り拓く神経創薬 招待

    井上 剛, 佐田 渚

    生物物理   56 ( 1 )   30 - 32   2016年

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  • 抗てんかん薬の創薬を目指して 招待

    井上 剛, 佐田 渚

    Epilepsy   10 ( 1 )   23 - 28   2016年

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  • 難治性てんかんケトン食療法のメカニズム 招待

    井上 剛, 佐田 渚

    Clinical Neuroscience   33   1431 - 1432   2015年

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  • 乳酸脱水素酵素を標的とし、てんかん発作を制御する 招待

    井上 剛, 佐田 渚

    細胞工学別冊・バイオ論文解説総集編1   32 - 33   2015年

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  • 乳酸脱水素酵素はてんかんの代謝的制御を可能にする創薬標的分子である 招待

    井上 剛, 佐田 渚

    実験医学   33 ( 14 )   2266 - 2268   2015年

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  • センサーを用いる薬物作用の<i>in situ</i>モニタリング 査読

    勝 孝, 駒越 圭子, 増田 和文, 加藤 久登, 井上 剛

    分析化学   62 ( 2 )   121 - 130   2013年

  • ダイナミッククランプ法を用いて神経回路網を操作する 招待

    井上 剛, 井本 敬二

    日本神経回路学会誌   15   117 - 125   2008年

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