Updated on 2026/07/27

写真a

 
HISHIDA Ryuichi
 
Organization
Brain Research Institute Field for Evolutionary Brain Pathology Dept. of Neuroscience of Disease Associate Professor
Title
Associate Professor
External link

Degree

  • 博士(理学) ( 1997.3   京都大学 )

  • 修士(理学) ( 1992.3   京都大学 )

Research Interests

  • フラビン蛋白蛍光イメージング

  • 脳機能イメージング

  • 高次連合野

  • マウス

  • ゼブラフィッシュ

  • 脳生理学

  • 病態生理学

  • 老化

  • アフリカメダカ

  • ミトコンドリア

  • 加齢関連疾患

Research Areas

  • Life Science / Neuroscience-general

  • Life Science / Molecular biology

Research History (researchmap)

  • 新潟大学 脳研究所 生命科学リソース研究センター / 脳科学リソース研究部門 脳病態解析分野   准教授

    2020.4

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  • Niigata University   Brain Research Institute Basic Neuroscience Branch Department of Neurophysiology   Associate Professor

    2007.7 - 2020.3

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  • Niigata University   Brain Research Institute Basic Neuroscience Branch Department of Neurophysiology   Assistant Professor

    1999.4 - 2007.6

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Research History

  • Niigata University   Dept. of Neuroscience of Disease, Field for Evolutionary Brain Pathology, Brain Research Institute   Associate Professor

    2026.4

  • Niigata University   Brain Research Institute Center for Bioresources   Associate Professor

    2020.4 - 2026.3

  • Niigata University   Brain Research Institute Basic Neuroscience Branch   Associate Professor

    2007.7 - 2020.3

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control   Associate Professor

    2007.7 - 2020.3

  • Niigata University   Graduate School of Medical and Dental Sciences Biomedical Sciences   Associate Professor

    2007.7 - 2020.3

  • Niigata University   Brain Research Institute Basic Neuroscience Branch   Assistant Professor

    1999.4 - 2007.6

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Education

  • 京都大学大学院   理学研究科 博士後期課程 (生物物理学専攻)

    1992.4 - 1997.3

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  • 京都大学大学院   理学研究科 修士課程 (生物物理学専攻)

    1990.4 - 1992.3

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  • 京都大学 理学部

    1986.4 - 1990.3

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Professional Memberships

 

Papers

  • Transcranial Calcium Macro-Imaging From the Auditory Cortex of Thy1-Cre-Driven GCaMP8 Transgenic Rats Reviewed

    Manavu Tohmi, Hisaaki Namba, Meiko Kawamura, Ryuichi Hishida, Shota Iguchi, Kazuto Kobayashi, Natsuki Matsushita, Tomoji Mashimo, Rie Natsume, Kenji Sakimura, Hiroyuki Nawa

    Neuropsychopharmacol Rep.   46 ( 2 )   e70113   2026.4

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    DOI: 10.1002/npr2.70113

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  • Homozygous slc25a20 Zebrafish Mutant Reveals Insights into Carnitine-Acylcarnitine Translocase Deficiency Pathogenesis. Reviewed

    Ryuichi Hishida, Kohei Ishiguro, Tomoyuki Yamanaka, Shinya Toyokuni, Hideaki Matsui

    Molecular Genetics and Metabolism Reports   41   101165 - 101165   2024.12

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    DOI: 10.1016/j.ymgmr.2024.101165

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  • GPATCH4 contributes to nucleolus morphology and its dysfunction impairs cell viability Reviewed

    Kazuki Kodera, Ryuichi Hishida, Akiko Sakai, Hiromi Nyuzuki, Noriko Matsui, Tomoyuki Yamanaka, Akihiko Saitoh, Hideaki Matsui

    Biochemical and Biophysical Research Communications   693   149384 - 149384   2024.1

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    DOI: 10.1016/j.bbrc.2023.149384

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  • Visualization of cortical activation in human brain by flavoprotein fluorescence imaging. Reviewed International journal

    Daiju Mitsuhashi, Ryuichi Hishida, Makoto Oishi, Tetsuya Hiraishi, Manabu Natsumeda, Katsuei Shibuki, Yukihiko Fujii

    Journal of neurosurgery   1 - 9   2022.2

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    OBJECTIVE: To develop an innovative brain mapping and neuromonitoring method during neurosurgery, the authors set out to establish intraoperative flavoprotein fluorescence imaging (iFFI) to directly visualize cortical activations in human brain. The significance of iFFI was analyzed by comparison with intraoperative perfusion-dependent imaging (iPDI), which is considered the conventional optical imaging, and by performing animal experiments. METHODS: Seven patients with intracerebral tumors were examined by iFFI and iPDI following craniotomy, using a single operative microscope equipped with a laser light source for iFFI and xenon lamp for iPDI. Images were captured by the same charge-coupled device camera. Responses to bipolar stimulation at selected points on the cortical surface were analyzed off-line, and relative signal changes were visualized by overlaying pseudocolor intensity maps onto cortical photographs. Signal changes exceeding 3 SDs from baseline were defined as significant. The authors also performed FFI and PDI on 10 mice using similar settings, and then compared signal patterns to intraoperative studies. RESULTS: Signals acquired by iFFI exhibited biphasic spatiotemporal changes consisting of an early positive signal peak (F1) and a delayed negative signal peak (F2). In contrast, iPDI signals exhibited only 1 negative peak (P1) that was significantly delayed compared to F1 (p < 0.02) and roughly in phase with F2. Compared to F2 and P1, F1 was of significantly lower amplitude (p < 0.02) and located closer to the bipolar stimulus center (p < 0.03), whereas F2 and P1 were more widespread, irregular, and partially overlapping. In mice, the spatiotemporal characteristics of FFI and PDI resembled those of iFFI and iPDI, but the early positive signal was more robust than F1. CONCLUSIONS: This is the first report in humans of successful intraoperative visualization of cortical activations by using iFFI, which showed rapid evoked cortical activity prior to perfusion-dependent signal changes. Further technical improvements can lead to establishment of iFFI as a real-time intraoperative tool.

    DOI: 10.3171/2022.1.JNS212542

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  • Auditory cortical activity elicited by infrared laser irradiation from the outer ear in Mongolian gerbils. Reviewed International journal

    Yuta Tamai, Yuki Ito, Takafumi Furuyama, Kensuke Horinouchi, Nagomi Murashima, Itsuki Michimoto, Ryuichi Hishida, Katsuei Shibuki, Shizuko Hiryu, Kohta I Kobayasi

    PloS one   15 ( 10 )   e0240227   2020

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    Infrared neural stimulation has been studied for its potential to replace an electrical stimulation of a cochlear implant. No studies, however, revealed how the technic reliably evoke auditory cortical activities. This research investigated the effects of cochlear laser stimulation from the outer ear on auditory cortex using brain imaging of activity-dependent changes in mitochondrial flavoprotein fluorescence signal. An optic fiber was inserted into the gerbil's ear canal to stimulate the lateral side of the cochlea with an infrared laser. Laser stimulation was found to activate the identified primary auditory cortex. In addition, the temporal profile of the laser-evoked responses was comparable to that of the auditory responses. Our results indicate that infrared laser irradiation from the outer ear has the capacity to evoke, and possibly manipulate, the neural activities of the auditory cortex and may substitute for the present cochlear implants in future.

    DOI: 10.1371/journal.pone.0240227

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  • Reciprocal connectivity between secondary auditory cortical field and amygdala in mice. Reviewed International journal

    Tsukano H, Hou X, Horie M, Kitaura H, Nishio N, Hishida R, Takahashi K, Kakita A, Takebayashi H, Sugiyama S, Shibuki K

    Scientific reports   9 ( 1 )   19610 - 19610   2019.12

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    Recent studies have examined the feedback pathway from the amygdala to the auditory cortex in conjunction with the feedforward pathway from the auditory cortex to the amygdala. However, these connections have not been fully characterized. Here, to visualize the comprehensive connectivity between the auditory cortex and amygdala, we injected cholera toxin subunit b (CTB), a bidirectional tracer, into multiple subfields in the mouse auditory cortex after identifying the location of these subfields using flavoprotein fluorescence imaging. After injecting CTB into the secondary auditory field (A2), we found densely innervated CTB-positive axon terminals that were mainly located in the lateral amygdala (La), and slight innervations in other divisions such as the basal amygdala. Moreover, we found a large number of retrogradely-stained CTB-positive neurons in La after injecting CTB into A2. When injecting CTB into the primary auditory cortex (A1), a small number of CTB-positive neurons and axons were visualized in the amygdala. Finally, we found a near complete absence of connections between the other auditory cortical fields and the amygdala. These data suggest that reciprocal connections between A2 and La are main conduits for communication between the auditory cortex and amygdala in mice.

    DOI: 10.1038/s41598-019-56092-9

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  • Associative responses to visual shape stimuli in the mouse auditory cortex Reviewed

    Ogi M, Yamagishi T, Tsukano H, Nishio N, Hishida R, Takahashi K, Horii A, Shibuki K

    PLoS One   14 ( 10 )   e0223242   2019.9

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  • Acute spatial spread of NO-mediated potentiation during hindpaw ischaemia in mice. Reviewed International journal

    Onishi T, Watanabe T, Sasaki M, Kamiya Y, Horie M, Tsukano H, Hishida R, Kohno T, Takebayashi H, Baba H, Shibuki K

    The Journal of physiology   597 ( 13 )   3441 - 3455   2019.5

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    KEY POINTS: Neuropathic pain spreads spatially beyond the injured sites, and the mechanism underlying the spread has been attributed to inflammation occurring in the spinal cord. However, the spatial spread of spinal/cortical potentiation induced by conduction block of the peripheral nerves can be observed prior to inflammation. In the present study, we found that spreading potentiation and hypersensitivity acutely induced by unilateral hindpaw ischaemia are nitric oxide (NO)-dependent and that NO is produced by ischaemia and quickly diffuses within the spinal cord. We also found that NO production induced by ischaemia is not observed in the presence of an antagonist for group II metabotropic glutamate receptors (mGluRs) and that neuronal NO synthase-positive dorsal horn neurons express group II mGluRs. These results suggest strongly that NO-mediated spreading potentiation in the spinal cord is one of the trigger mechanisms for neuropathic pain. ABSTRACT: Cortical/spinal responses to hindpaw stimulation are bilaterally potentiated by unilateral hindpaw ischaemia in mice. We tested the hypothesis that hindpaw ischaemia produces nitric oxide (NO), which diffuses in the spinal cord to induce spatially spreading potentiation. Using flavoprotein fluorescence imaging, we confirmed that the spreading potentiation in hindpaw responses was induced during ischaemia in the non-stimulated hindpaw. This spreading potentiation was blocked by spinal application of l-NAME, an inhibitor of NO synthase (NOS). Furthermore, no spreading potentiation was observed in neural NOS (nNOS) knockout mice. Spinal application of an NO donor was enough to induce cortical potentiation and mechanical hypersensitivity. The spatial distribution of NO during unilateral hindpaw ischaemia was visualized using 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM). An increase in fluorescence derived from the complex of DAF-FM with NO was observed on the ischaemic side of the spinal cord. A similar but smaller increase was also observed on the contralateral side. Somatosensory potentiation after hindpaw ischaemia is known to be inhibited by spinal application of LY354740, an agonist of group II metabotropic glutamate receptors (mGluRs). We confirmed that the spinal DAF-FM fluorescence increases during hindpaw ischaemia were not observed in the presence of LY354740. We also confirmed that approximately half of the nNOS-positive neurons in the superficial laminae of the dorsal horn expressed mGluR2 mRNA. These results suggest that disinhibition of mGluR2 produces NO which in turn induces a spreading potentiation in a wide area of the spinal cord. Such spreading, along with the consequent non-specific potentiation in the spinal cord, may trigger neuropathic pain.

    DOI: 10.1113/JP277615

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  • Feedback inhibition derived from the posterior parietal cortex regulates the neural properties of the mouse visual cortex. Reviewed International journal

    Hishida R, Horie M, Tsukano H, Tohmi M, Yoshitake K, Meguro R, Takebayashi H, Yanagawa Y, Shibuki K

    The European journal of neuroscience   50 ( 6 )   2970 - 2987   2019.4

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    Feedback regulation from the higher association areas is thought to control the primary sensory cortex, contribute to the cortical processing of sensory information, and work for higher cognitive functions such as multimodal integration and attentional control. However, little is known about the underlying neural mechanisms. Here, we show that the posterior parietal cortex (PPC) persistently inhibits the activity of the primary visual cortex (V1) in mice. Activation of the PPC causes the suppression of visual responses in V1 and induces the short-term depression, which is specific to visual stimuli. In contrast, pharmacological inactivation of the PPC or disconnection of cortical pathways from the PPC to V1 results in an effect of transient enhancement of visual responses in V1. Two-photon calcium imaging demonstrated that the cortical disconnection caused V1 excitatory neurons an enhancement of visual responses and a reduction of orientation selectivity index (OSI). These results show that the PPC regulates the response properties of V1 excitatory neurons. Our findings reveal one of the functions of the PPC, which may contribute to higher brain functions in mice.

    DOI: 10.1111/ejn.14424

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  • Direct Relay Pathways from Lemniscal Auditory Thalamus to Secondary Auditory Field in Mice. Reviewed

    Ohga S, Tsukano H, Horie M, Terashima H, Nishio N, Kubota Y, Takahashi K, Hishida R, Takebayashi H, Shibuki K

    Cerebral cortex (New York, N.Y. : 1991)   2018.10

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    DOI: 10.1093/cercor/bhy234

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  • Higher visual responses in the temporal cortex of mice. Reviewed International journal

    Nishio N, Tsukano H, Hishida R, Abe M, Nakai J, Kawamura M, Aiba A, Sakimura K, Shibuki K

    Scientific reports   8 ( 1 )   11136 - 11136   2018.7

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    The visual cortex of mice is a useful model for investigating the mammalian visual system. In primates, higher visual areas are classified into two parts, the dorsal stream ("where" pathway) and ventral stream ("what" pathway). The ventral stream is known to include a part of the temporal cortex. In mice, however, some cortical areas adjacent to the primary visual area (V1) in the occipital cortex are thought to be comparable to the ventral stream in primates, although the whole picture of the mouse ventral stream has never been elucidated. We performed wide-field Ca2+ imaging in awake mice to investigate visual responses in the mouse temporal cortex, and found that the postrhinal cortex (POR), posterior to the auditory cortex (AC), and the ectorhinal and temporal association cortices (ECT), ventral to the AC, showed clear visual responses to moving visual objects. The retinotopic maps in the POR and ECT were not clearly observed, and the amplitudes of the visual responses in the POR and ECT were less sensitive to the size of the objects, compared to visual responses in the V1. In the ECT, objects of different sizes activated different subareas. These findings strongly suggest that the mouse ventral stream extends to the ECT ventral to the AC, and that it has characteristic response properties that are markedly different from the response properties in the V1.

    DOI: 10.1038/s41598-018-29530-3

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  • Molecular diversity of clustered protocadherin-α required for sensory integration and short-term memory in mice. Reviewed

    Yamagishi T, Yoshitake K, Kamatani D, Watanabe K, Tsukano H, Hishida R, Takahashi K, Takahashi S, Horii A, Yagi T, Shibuki K

    Scientific reports   8 ( 1 )   9616   2018.6

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    DOI: 10.1038/s41598-018-28034-4

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    Other Link: http://www.nature.com/articles/s41598-018-28034-4

  • Tomographic optical imaging of cortical responses after crossing nerve transfer in mice. Reviewed

    Maniwa K, Yamashita H, Tsukano H, Hishida R, Endo N, Shibata M, Shibuki K

    PloS one   13 ( 2 )   e0193017   2018

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    DOI: 10.1371/journal.pone.0193017

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  • Reconsidering Tonotopic Maps in the Auditory Cortex and Lemniscal Auditory Thalamus in Mice Reviewed

    Hiroaki Tsukano, Masao Horie, Shinpei Ohga, Kuniyuki Takahashi, Yamato Kubota, Ryuichi Hishida, Hirohide Takebayashi, Katsuei Shibuki

    FRONTIERS IN NEURAL CIRCUITS   11   14   2017.2

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  • Corrigendum: Reconsidering Tonotopic Maps in the Auditory Cortex and Lemniscal Auditory Thalamus in Mice Reviewed

    Hiroaki Tsukano, Masao Horie, Shinpei Ohga, Kuniyuki Takahashi, Yamato Kubota, Ryuichi Hishida, Hirohide Takebayashi, Katsuei Shibuki

    Frontiers in neural circuits   11   39   2017.1

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    DOI: 10.3389/fncir.2017.00039

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  • Independent tonotopy and thalamocortical projection patterns in two adjacent parts of the classical primary auditory cortex in mice Reviewed

    Hiroaki Tsukano, Masao Horie, Kuniyuki Takahashi, Ryuichi Hishida, Hirohide Takebayashi, Katsuei Shibuki

    NEUROSCIENCE LETTERS   637   26 - 30   2017.1

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    DOI: 10.1016/j.neulet.2016.11.062

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  • Auditory cortical field coding long-lasting tonal offsets in mice. Reviewed

    Baba H, Tsukano H, Hishida R, Takahashi K, Horii A, Takahashi S, Shibuki K

    Scientific reports   6 ( 1 )   34421   2016.9

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    DOI: 10.1038/srep34421

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    Other Link: http://www.nature.com/articles/srep34421.pdf

  • Quantitative map of multiple auditory cortical regions with a stereotaxic fine-scale atlas of the mouse brain. Reviewed

    Tsukano H, Horie M, Hishida R, Takahashi K, Takebayashi H, Shibuki K

    Scientific reports   6   22315   2016.2

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    DOI: 10.1038/srep22315

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  • Spinal mechanisms underlying potentiation of hindpaw responses observed after transient hindpaw ischemia in mice. Reviewed International journal

    Watanabe T, Sasaki M, Komagata S, Tsukano H, Hishida R, Kohno T, Baba H, Shibuki K

    Scientific reports   5   11191 - 11191   2015.7

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    Transient ischemia produces postischemic tingling sensation. Ischemia also produces nerve conduction block that may modulate spinal neural circuits. In the present study, reduced mechanical thresholds for hindpaw-withdrawal reflex were found in mice after transient hindpaw ischemia, which was produced by a high pressure applied around the hindpaw for 30 min. The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors. Neural activities in the spinal cord and the primary somatosensory cortex (S1) were investigated using activity-dependent changes in endogenous fluorescence derived from mitochondrial flavoproteins. Ischemic treatment induced potentiation of the ipsilateral spinal and contralateral S1 responses to hindpaw stimulation. Both types of potentiation were blocked by spinal application of LY354740. The contralateral S1 responses, abolished by lesioning the ipsilateral dorsal column, reappeared after ischemic treatment, indicating that postischemic tingling sensation reflects a sensory modality shift from tactile sensation to nociception in the spinal cord. Changes in neural responses were investigated during ischemic treatment in the contralateral spinal cord and the ipsilateral S1. Potentiation already appeared during ischemic treatment for 30 min. The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

    DOI: 10.1038/srep11191

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  • Delineation of a frequency-organized region isolated from the mouse primary auditory cortex. Reviewed

    Tsukano H, Horie M, Bo T, Uchimura A, Hishida R, Kudoh M, Takahashi K, Takebayashi H, Shibuki K

    Journal of neurophysiology   113 ( 7 )   2900 - 20   2015.4

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    DOI: 10.1152/jn.00932.2014

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  • Impaired clustered protocadherin-α leads to aggregated retinogeniculate terminals and impaired visual acuity in mice. Reviewed International journal

    Meguro R, Hishida R, Tsukano H, Yoshitake K, Imamura R, Tohmi M, Kitsukawa T, Hirabayashi T, Yagi T, Takebayashi H, Shibuki K

    Journal of neurochemistry   133 ( 1 )   66 - 72   2015.4

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    Clustered protocadherins (cPcdhs) comprising cPcdh-α, -β, and -γ, encode a large family of cadherin-like cell-adhesion molecules specific to neurons. Impairment of cPcdh-α results in abnormal neuronal projection patterns in specific brain areas. To elucidate the role of cPcdh-α in retinogeniculate projections, we investigated the morphological patterns of retinogeniculate terminals in the lateral geniculate (LG) nucleus of mice with impaired cPcdh-α. We found huge aggregated retinogeniculate terminals in the dorsal LG nucleus, whereas no such aggregated terminals derived from the retina were observed in the olivary pretectal nucleus and the ventral LG nucleus. These aggregated terminals appeared between P10 and P14, just before eye opening and at the beginning of the refinement stage of the retinogeniculate projections. Reduced visual acuity was observed in adult mice with impaired cPcdh-α, whereas the orientation selectivity and direction selectivity of neurons in the primary visual cortex were apparently normal. These findings suggest that cPcdh-α is required for adequate spacing of retinogeniculate projections, which may be essential for normal development of visual acuity.

    DOI: 10.1111/jnc.13053

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  • Multimodal cortical sensory pathways revealed by sequential transcranial electrical stimulation in mice. Reviewed

    Hishida R, Kudoh M, Shibuki K

    Neuroscience research   87   49 - 55   2014.10

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    DOI: 10.1016/j.neures.2014.07.004

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  • The Extrageniculate Visual Pathway Generates Distinct Response Properties in the Higher Visual Areas of Mice Reviewed

    Manavu Tohmi, Reiko Meguro, Hiroaki Tsukano, Ryuichi Hishida, Katsuei Shibuki

    CURRENT BIOLOGY   24 ( 6 )   587 - 597   2014.3

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    DOI: 10.1016/j.cub.2014.01.061

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  • Visual map shifts based on whisker-guided cues in the young mouse visual cortex Reviewed

    Kohei Yoshitake, Hiroaki Tsukano, Manavu Tohmi, Seiji Komagata, Ryuichi Hishida, Takeshi Yagi, Katsuei Shibuki

    Cell Reports   5 ( 5 )   1365 - 1374   2013.12

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    DOI: 10.1016/j.celrep.2013.11.006

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  • Age-related deterioration of cortical responses to slow FM sounds in the auditory belt region of adult C57BL/6 mice Reviewed

    Hiroaki Tsukano, Masao Horie, Yuusuke Honma, Shinpei Ohga, Ryuichi Hishida, Hirohide Takebayashi, Sugata Takahashi, Katsuei Shibuki

    NEUROSCIENCE LETTERS   556   204 - 209   2013.11

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    DOI: 10.1016/j.neulet.2013.10.015

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  • Dual compartments of the ventral division of the medial geniculate body projecting to the core region of the auditory cortex in C57BL/6 mice Reviewed

    Masao Horie, Hiroaki Tsukano, Ryuichi Hishida, Hirohide Takebayashi, Katsuei Shibuki

    NEUROSCIENCE RESEARCH   76 ( 4 )   207 - 212   2013.8

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    DOI: 10.1016/j.neures.2013.05.004

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  • Auditory Cortical Areas Activated by Slow Frequency-Modulated Sounds in Mice Reviewed

    Yuusuke Honma, Hiroaki Tsukano, Masao Horie, Shinsuke Ohshima, Manavu Tohmi, Yamato Kubota, Kuniyuki Takahashi, Ryuichi Hishida, Sugata Takahashi, Katsuei Shibuki

    PLOS ONE   8 ( 7 )   e68113   2013.7

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    DOI: 10.1371/journal.pone.0068113

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  • Restoration of Contralateral Representation in the Mouse Somatosensory Cortex after Crossing Nerve Transfer Reviewed

    Haruyoshi Yamashita, Shanlin Chen, Seiji Komagata, Ryuichi Hishida, Takuji Iwasato, Shigeyoshi Itohara, Takeshi Yagi, Naoto Endo, Minoru Shibata, Katsuei Shibuki

    PLOS ONE   7 ( 4 )   e35676   2012.4

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    DOI: 10.1371/journal.pone.0035676

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  • Detection of virtual pitch up to 5 kHz by mice Reviewed

    Hiroaki Tsukano, Ryuichi Hishida, Katsuei Shibuki

    NEUROSCIENCE RESEARCH   71 ( 2 )   140 - 144   2011.10

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    DOI: 10.1016/j.neures.2011.06.005

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  • Transcranial electrical stimulation of cortico-cortical connections in anesthetized mice Reviewed

    Ryuichi Hishida, Kenji Watanabe, Masaharu Kudoh, Katsuei Shibuki

    JOURNAL OF NEUROSCIENCE METHODS   201 ( 2 )   315 - 321   2011.10

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    DOI: 10.1016/j.jneumeth.2011.08.007

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  • Nociceptive cortical responses during capsaicin-induced tactile allodynia in mice with spinal dorsal column lesioning Reviewed

    Seiji Komagata, Keisuke Tamaki, Ryuichi Hishida, Nobuaki Takeshita, Katsuei Shibuki

    NEUROSCIENCE RESEARCH   69 ( 4 )   348 - 351   2011.4

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    DOI: 10.1016/j.neures.2011.01.005

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  • Initial phase of neuropathic pain within a few hours after nerve injury in mice. Reviewed

    Komagata Seiji, Chen Shanlin, Suzuki Akiko, Yamashita Haruyoshi, Hishida Ryuichi, Maeda Takeyasu, Shibata Minoru, Shibuki Katsuei

    J Neurosci   31 ( 13 )   4896 - 4905   2011.3

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    DOI: 10.1523/JNEUROSCI.6753-10.2011

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  • Timing-dependent effects of whisker trimming in thalamocortical slices including the mouse barrel cortex. Reviewed

    Watanabe K, Kamatani D, Hishida R, Shibuki K

    Brain Res   1385   93 - 106   2011

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    DOI: 10.1016/j.brainres.2011.02.026

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  • Cortical depression in the mouse auditory cortex after sound discrimination learning Reviewed

    Shinsuke Ohshima, Hiroaki Tsukano, Yamato Kubota, Kuniyuki Takahashi, Ryuichi Hishida, Sugata Takahashi, Katsuei Shibuki

    NEUROSCIENCE RESEARCH   67 ( 1 )   51 - 58   2010.5

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    DOI: 10.1016/j.neures.2010.01.005

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  • Transcranial imaging of somatotopic map plasticity after tail cut in mice Reviewed

    Hiroki Kitaura, Ryuichi Hishida, Katsuei Shibuki

    BRAIN RESEARCH   1319   54 - 59   2010.3

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    DOI: 10.1016/j.brainres.2010.01.020

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  • Spinal plasticity converting tactile inputs to pain within a few hours after disruption of GDNF-induced low frequency firing in tactile nerves Reviewed

    Seiji Komagata, Shanlin Chen, Akiko Suzuki, Haruyoshi Yamashita, Ryuichi Hishida, Takeyasu Maeda, Minoru Shibata, Katsuei Shibuki

    NEUROSCIENCE RESEARCH   68   E156 - E156   2010

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  • Imaging of somatosensory cortical responses elicited by neuropathic pain in mice Reviewed

    Katsuei Shibuki, Seiji Komagata, Shanlin Chen, Akiko Suzuki, Haruyoshi Yamashita, Ryuichi Hishida, Takeyasu Maeda, Minoru Shibata

    NEUROSCIENCE RESEARCH   68   E30 - E30   2010

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  • Flavoprotein fluorescence imaging of experience-dependent cortical plasticity in rodents. Reviewed

    Katsuei Shibuki, Ryuichi Hishida, Manavu Tohmi, Kuniyuki Takahashi, Hiroki Kitaura, Yamato Kubota

    In Vivo Optical Imaging of Brain Function. 2nd edition. (Frostig RD, ed), Chapter 7, Frontiers in Neuroscience   193 - 220   2009.5

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  • Transcranial flavoprotein fluorescence imaging of mouse cortical activity and plasticity Reviewed

    Manavu Tohmi, Kuniyuki Takahashi, Yamato Kubota, Ryuichi Hishida, Katsuei Shibuki

    JOURNAL OF NEUROCHEMISTRY   109 ( Suppl 1 )   3 - 9   2009.5

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    DOI: 10.1111/j.1471-4159.2009.05926.x

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  • Transcranial photo-inactivation of neural activities in the mouse auditory cortex Reviewed

    Yamato Kubota, Daiki Kamatani, Hiroaki Tsukano, Shinsuke Ohshima, Kuniyuki Takahashi, Ryuichi Hishida, Masaharu Kudoh, Sugata Takahashi, Katsuei Shibuki

    NEUROSCIENCE RESEARCH   60 ( 4 )   422 - 430   2008.4

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    DOI: 10.1016/j.neures.2007.12.013

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  • Long-term depression induced by local tetanic stimulation in the rat auditory cortex Reviewed

    Kenji Watanabe, Daiki Kamatani, Ryuichi Hishida, Masaharu Kudoh, Katsuei Shibuki

    BRAIN RESEARCH   1166   20 - 28   2007.8

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    DOI: 10.1016/j.brainres.2007.06.049

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  • Experience-dependent formation of activity propagation patterns at the somatosensory S1 and S2 boundary in rat cortical slices Reviewed

    Dalki Kamatani, Ryuichi Hishida, Masaharu Kudoh, Katsuei Shibuki

    NEUROIMAGE   35 ( 1 )   47 - 57   2007.3

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    DOI: 10.1016/j.neuroimage.2006.08.049

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  • Functional local connections with differential activity-dependence and critical periods surrounding the primary auditory cortex in rat cerebral slices Reviewed

    Ryuichi Hishida, Daiki Kamatani, Hiroki Kitaura, Masaharu Kudoh, Katsuei Shibuki

    NEUROIMAGE   34 ( 2 )   679 - 693   2007.1

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    DOI: 10.1016/j.neuroimage.2006.09.030

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  • Coupling of brain function and metabolism: Endogenous flavoprotein fluorescence imaging of neural activities by local changes in energy metabolism Reviewed

    K. Shibuki, R. Hishida, H. Kitaura, K. Takahashi, M. Tohmi

    Handbook of Neurochemistry and Molecular Neurobiology: Brain Energetics. Integration of Molecular and Cellular Processes   5   321 - 342   2007

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    DOI: 10.1007/978-0-387-30411-3_13

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  • Requirement of the auditory association cortex for discrimination of vowel-like sounds in rats Reviewed

    Masaharu Kudoh, Yoko Nakayama, Ryuichi Hishida, Katsuei Shibuki

    NEUROREPORT   17 ( 17 )   1761 - 1766   2006.11

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    DOI: 10.1097/WNR.0b013e32800fef9d

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  • Endogenous fluorescence imaging of somatosensory cortical activities after discrimination learning in rats Reviewed

    K Shibuki, K Ono, R Hishida, M Kudoh

    NEUROIMAGE   30 ( 3 )   735 - 744   2006.4

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    DOI: 10.1016/j.neuroimage.2005.10.004

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  • Transcranial fluorescence imaging of auditory cortical plasticity regulated by acoustic environments in mice Reviewed

    K Takahashi, R Hishida, Y Kubota, M Kudoh, S Takahashi, K Shibuki

    EUROPEAN JOURNAL OF NEUROSCIENCE   23 ( 5 )   1365 - 1376   2006.3

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    DOI: 10.1111/j.1460-9568.2006.04662.x

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  • Short-term plasticity visualized with flavoprotein autofluorescence in the somatosensory cortex of anaesthetized rats Reviewed

    H Murakami, D Kamatani, R Hishida, T Takao, M Kudoh, T Kawaguchi, R Tanaka, K Shibuki

    EUROPEAN JOURNAL OF NEUROSCIENCE   19 ( 5 )   1352 - 1360   2004.3

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    DOI: 10.1111/j.1460-9568.2004.03237.x

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  • Activity-dependent persisting modification of polysynaptic neural circuits involving layer V pyramidal neurons in rat auditory cortex in vitro Reviewed

    H Kitaura, R Hishida, M Kudoh, K Shibuki

    EUROPEAN JOURNAL OF NEUROSCIENCE   19 ( 2 )   356 - 364   2004.1

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    DOI: 10.1111/j.1460-9568.2003.03136.x

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  • Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence Reviewed

    K Shibuki, R Hishida, H Murakami, M Kudoh, T Kawaguchi, M Watanabe, S Watanabe, T Kouuchi, R Tanaka

    JOURNAL OF PHYSIOLOGY-LONDON   549 ( 3 )   919 - 927   2003.6

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    DOI: 10.1113/jphysiol.2003.040709

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  • Anisotropic functional connections between the auditory cortex and area 18a in rat cerebral slices Reviewed

    R Hishida, K Hoshino, M Kudoh, M Norita, K Shibuki

    NEUROSCIENCE RESEARCH   46 ( 2 )   171 - 182   2003.6

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    DOI: 10.1016/S0168-0102(03)00059-2

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  • hch-1, a gene required for normal hatching and normal migration of a neuroblast in C-elegans, encodes a protein related to TOLLOID and BMP-1 Reviewed

    R Hishida, T Ishihara, K Kondo, Katsura, I

    EMBO JOURNAL   15 ( 16 )   4111 - 4122   1996.8

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  • THE ROLE OF ACIDIC RESIDUES IN THE FUSION SEGMENT OF INFLUENZA-A VIRUS HEMAGGLUTININ IN LOW-PH-DEPENDENT MEMBRANE-FUSION Reviewed

    E NOBUSAWA, R HISHIDA, M MURATA, K KAWASAKI, S OHNISHI, K NAKAJIMA

    ARCHIVES OF VIROLOGY   140 ( 5 )   865 - 875   1995

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    DOI: 10.1007/BF01314963

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  • SPECIFICITY OF AMPHIPHILIC ANIONIC PEPTIDES FOR FUSION OF PHOSPHOLIPID-VESICLES Reviewed

    M MURATA, S TAKAHASHI, Y SHIRAI, S KAGIWADA, R HISHIDA, S OHNISHI

    BIOPHYSICAL JOURNAL   64 ( 3 )   724 - 734   1993.3

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  • INVITRO FUSION OF RABBIT LIVER GOLGI MEMBRANES WITH LIPOSOMES Reviewed

    S KAGIWADA, M MURATA, R HISHIDA, M TAGAYA, S YAMASHINA, S OHNISHI

    JOURNAL OF BIOLOGICAL CHEMISTRY   268 ( 2 )   1430 - 1435   1993.1

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  • INTERACTION OF THE GOLGI MEMBRANES ISOLATED FROM RABBIT LIVER WITH MICROTUBULES INVITRO Reviewed

    M MURATA, TJ ITOH, S KAGIWADA, R HISHIDA, H HOTANI, S OHNISHI

    BIOLOGY OF THE CELL   75 ( 2 )   127 - 134   1992

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  • MODIFICATION OF THE N-TERMINUS OF MEMBRANE FUSION-ACTIVE PEPTIDES BLOCKS THE FUSION ACTIVITY Reviewed

    M MURATA, S KAGIWADA, R HISHIDA, R ISHIGURO, S OHNISHI, S TAKAHASHI

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   179 ( 2 )   1050 - 1055   1991.9

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    DOI: 10.1016/0006-291X(91)91925-3

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MISC

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Research Projects

  • アフリカメダカで解く脳老化の空間構造:進化的に保存された加齢病態因子の探索と解析

    Grant number:26K09988

    2026.4 - 2030.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    菱田竜一

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  • アフリカメダカを使った加齢関連疾患の臓器特異的な病態因子の探索と解析

    Grant number:22K07020

    2022.4 - 2026.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    菱田 竜一

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  • 全脳神経活動可視化と光遺伝学による幻覚の脳神経メカニズムの探求

    Grant number:21K18242

    2021.7 - 2025.3

    System name:科学研究費助成事業

    Research category:挑戦的研究(開拓)

    Awarding organization:日本学術振興会

    那波 宏之, 菱田 竜一, 難波 寿明

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    Grant amount:\25610000 ( Direct Cost: \19700000 、 Indirect Cost:\5910000 )

    近年のヒト脳機能画像研究から、幻聴、幻覚に代表される感覚の偽認知には、一次もしくは周辺二次感覚皮質の異常発火が関与しているとされるが、この仮説を神経科学的に実証する手段はなかった。そこで、幻覚研究のための動物モデル確立とその評価のための計測システムの構築を目指し、GCAMPカルシウムセンサーを用いた脳活動可視化システムをモデル動物に適用し、幻聴や幻覚に対する大脳皮質活動パターンの特徴を捉える計画を立案した。
    初年度には、無感覚刺激下での大脳皮質活動をマクロレベルとミクロレベルで観測できるカルシウムイメージングシステムを、前者はBrainVISION社のマクロ蛍光顕微鏡THTシリーズ、後者はInscopix社内視鏡型蛍光顕微鏡NVueを基に構築した。実験対象となる高速型カルシウムセンサーGCAMP8を発現するTGラットの繁殖とその評価を行った。結果、当該TGラットは特異的なGCAMP8脳内発現制御が可能で、十分な神経活動依存的蛍光変化を呈することを確認できた。加えて、幻覚・幻聴に対する自発的神経活動が低シグナルである可能性も考慮して、高感度型GCAMP6Sを発現できるTGラットの作製に着手した。当該遺伝子発現ベクターを設計し、そのTGラットの作製を作製を外部委託した。幻覚誘発剤などによる大脳皮質活動変化のカルシウムイメージング実施するに先立ち、NMDA受容体阻害剤やドパミンアゴニストで誘発される自発的神経活動を計測中である。

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  • Experience-dependent switch in mechanisms for inhibitory neurons in cortical circuits processing.

    Grant number:20K06869

    2020.4 - 2023.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  • Circuit mechanisms of attentional interference by pain stimuli: analysis using mouse cortical imaging

    Grant number:18K06518

    2018.4 - 2022.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Hishida Ryuichi

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    Although it is known that pain stimuli interfere with the higher-order function of attention, the neural circuit mechanism of this interference is unknown. Therefore, we hypothesized that "there is a dense inhibitory projection from the association area network that processes pain information to each sensory cortex. And the sensory cortex inhibition by the retrograde projection is the mechanism of attentional interference by pain stimuli," and proceeded with the analysis using a technique called cortical imaging in anesthetized mice. The results showed that (1) the parietal association cortex routinely suppresses the somatosensory cortex's pain response, (2) the efficiency of sensory cortex suppression by the parietal association cortex varies according to modality, suggesting that the suppression mechanism differs, and (3) the frontal association cortex also routinely suppresses the somatosensory cortex's pain response.

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  • Functional analysis of the mouse posterior parietal cortex that forms the filter of selective attention

    Grant number:26430011

    2014.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Hishida Ryuichi

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    Grant amount:\5070000 ( Direct Cost: \3900000 、 Indirect Cost:\1170000 )

    Although we found that the feedback projection from the mouse posterior parietal cortex (PPC) to the primary visual cortex (V1) exists and suppresses V1, its physiological role was unknown. Therefore, we made a hypothesis that the projection from the PPC forms an initial selection filter of selective attention in V1, and proceeded with the analysis. We found that (1) the PPC has an ability to cause plastic changes in V1 responses to visual stimuli in a selective manner, (2) the PPC modifies the direction selectivity of excitatory neurons in V1, (3) the function of the V1 suppression is mapped to the PPC, etc. These results are supposed to support the hypothesis and encourage the further analysis.

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  • Analysis of the attentional mechanism in the mouse cingulate cortex

    Grant number:23500383

    2011 - 2013

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    HISHIDA Ryuichi

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    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

    It is thought that feedback projections from higher areas modulate sensory functions in the neocortex. However, it remains to be elucidated how higher areas modulate functions of the primary areas. To better understand the neural mechanisms, we studied properties of inhibitory projections from higher areas to the primary visual cortex (V1) in mice using transcranial flavoprotein fluorescence imaging. We investigated the functions of the feedback projections by blocking the pathways from the higher areas to V1. The acute blocking experiments indicated the presence of tonic inhibition mediated by the feedback projections. The chronic blockings resulted in a significant reduction of V1 response to grating stimuli with reduced contrasts. Tracer injections to the areas showed the presence of direct and indirect pathways. These observations strongly suggest that feedback inhibitory projections from the areas to V1 can adjust neural responses in V1 for keeping appropriate visual acuity.

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  • Neural circuits underlying sensory association functions in mice

    Grant number:22115011

    2010.4 - 2015.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Awarding organization:Japan Society for the Promotion of Science

    SHIBUKI Katsuei, HISHIDA Ryuichi, TOHMI Manavu, TSUKANO Hiroaki, WATANABE Kenji, YOSHITAKE Kohei

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    Grant amount:\88270000 ( Direct Cost: \67900000 、 Indirect Cost:\20370000 )

    The posterior parietal cortex (PPC) is a part of the higher visual cortices in the dorsal pathway. We found that PPC was responsible for the integration of spatial information obtained from the eyes and whiskers in mice. PPC was also responsible for short-term memory of visual spatial information. In contrast, higher visual cortices in the ventral pathway were responsible for short-term memory of shape information, and for the integration of visual and auditory information. These functions were dependent on clustered protocadherin alpha, neuro-specific cell adhesion molecules. It is suggested that common neural circuits, dependent on clustered protocadherins, work as short-term memory circuits to achieve these functions. The sensory information, kept as sustained neural activities in the circuits, is likely to induce related neural activities in the wide brain areas connected with higher visual cortices. The activity complex may be regarded as the neural correlate of visual awareness.

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  • Transcranial optical imaging of neural activity in deep brain structurtes in mice

    Grant number:22240044

    2010 - 2012

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    SHIBUKI Katsuei, HISHIDA Ryuichi, TOHMI Manabu

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    Grant amount:\51610000 ( Direct Cost: \39700000 、 Indirect Cost:\11910000 )

    We developed a new optical method for imaging neural activity in deep brain structures in mice. We used a macroconfocal microscope in a near-infrared range. Generally,a confocal microscope uses only a part of light passing through a tiny pinhole. Therefore,the diameter of a pinhole was expanded, and sensitivity of our macroconfocal microscopewas strengthened. We labeled red blood cells (RBC) with NIR815, a near-infraredfluorescent probe, and applied the fluorescent RBCs to mice. In these mice,activity-dependent hemodynamic responses elicited by visual stimuli were successfullyimaged in the lateral geniculate body, which located approximately 2.5 mm deep from thecortical surface.

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  • 逐次経頭蓋電気刺激法によるマウス頭頂連合野の機能解析

    2008.4 - 2010.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    菱田 竜一

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    Grant type:Competitive

    新たに開発した逐次経頭蓋電気刺激法による、マウス大脳皮質での感覚情報伝達経路の探索および解析。主に、視覚・聴覚・体性感覚という3つの異なるモダリティの感覚情報が統合される領野の探索。

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  • Neural mechanisms for perception of harmony in the auditory cortex

    Grant number:19200025

    2007 - 2009

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    SHIBUKI Katsuei, IWASATO Takuji, KUDOH Masaharu, YAGI Takeshi, HISHIDA Ryuichi, TOHMI Manabu

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    Grant amount:\49270000 ( Direct Cost: \37900000 、 Indirect Cost:\11370000 )

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  • Physiological functions and underlying cellular/molecular mechanisms of retrograde inputs from higher cortical areas toe sensory cortices

    Grant number:16200023

    2004 - 2006

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    SHIBUKI Katsuei, MUDOH Masaharu, HISHIDA Ryuichi

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    Grant amount:\49530000 ( Direct Cost: \38100000 、 Indirect Cost:\11430000 )

    Using transcranial flavoprotein fluorescence imaging in mice, the following results have been obtained.
    1. We investigated auditory cortical plasticity regulated by acoustic environments. Mice were reared in various acoustic environments for at least 4 weeks after birth. Cortical responses elicited by tonal stimuli (5, 10 and 20 kHz) exhibited tonotopic maps in the primary auditory cortex (AI). Depression of auditory cortical responses was observed in sound-deprived mice compared with naive mice reared in a normal acoustic environment. When mice were exposed to an environmental tonal stimulus at 10 kHz for more than 4 weeks after birth, the cortical responses were potentiated in a frequency-specific manner. These results suggest that acoustic environments regulate the development of intracortical circuits in the mouse auditory cortex.
    2. We visualized cortical responses to missing fundamentals in mice. The activity patterns in AI elicited by 5 kHz were different from those elicited by 20 kHz or 25 kHz. However, the areas activated by 5 kHz were also activated by the mixture of 20 kHz plus 25 kHz but not by that of 19 kHz plus 26 kHz, suggesting that cortical responses to missing fundamentals in AI were visualized using flavoprotein fluorescence imaging
    3. Experience-dependent plasticity in the visual cortex was investigated. After monocular deprivation (MD) of 4 days starting from P28, deprived eye responses were suppressed compared to non-deprived eye responses in the binocular zone, but not in the monocular zone. Imaging faithfully recapitulated a critical period for plasticity with maximal effects of MD observed around P28 and not in adulthood even under urethane anesthesia. These results indicate that transcranial flavoprotein fluorescence imaging is a powerful tool for investigating experience-dependent plasticity in the mouse visual cortex.
    4. We designed a hemilateral prism goggle for mice. This goggle was attached on the skull of mice during the critical period. The visual cortical responses elicited via the eye with a prism were significantly suppressed compared with those elicited via the contralateral normal eye. However, this suppression was not observed in mice, in which whiskers were trimmed. It was suggested that the visual responses might be suppressed by multimodal sensory mismatching between somatosensory inputs and visual inputs regarding spatial recognition.

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  • Mechanisms of sound sequence discrimination learning motivated by reward in the rat

    Grant number:16500197

    2004 - 2005

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    KUDOH Masaharu, HISHIDA Ryuichi

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    Grant amount:\3600000 ( Direct Cost: \3600000 )

    We have previously reported that sound sequence discrimination learning requires cholinergic inputs to the auditory cortex (AC) in rats. In that study, reward was used for motivating discrimination behavior in rats. Therefore, dopaminergic inputs mediating reward signals may have an important role in the learning. We tested the possibility in the present study. Rats were trained to discriminate sequences of two sound components, and licking behavior in response to one of the two sequences was rewarded with water. To identify the dopaminergic inputs responsible for the learning, dopaminergic afferents to the AC were lesioned with local injection of 6-hydroxydopamine (6-OHDA). The injection attenuated sound sequence discrimination learning, while it had no effect on discrimination between the sound components of the sequence stimuli. Local injection of 6-OHDA into the nucleus accumbens attenuated sound discrimination learning. However, not only discrimination learning of sound sequence but also that of the sound components were impaired. SCH23390 (0.2mg/kg, i.p.), a D1 receptor antagonist, had no effect on sound sequence discrimination learning, while it attenuated the licking behavior to unfamiliar stimuli. Haloperidol (0.5 mg/kg, i.p.), a D2 family antagonist, attenuated sound sequence discrimination learning, while it had no clear suppressive effect on discrimination of two different sound components and licking. These results suggest that D2 family receptors activated by dopaminergic inputs to the AC are required for sound sequence discrimination learning.

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  • ラット視覚野・聴覚野に隣接する高次領野を介した視聴覚連合機構の解析

    2002.4 - 2005.3

    System name:科学研究費助成事業

    Research category:若手研究(B)

    Awarding organization:日本学術振興会

    菱田 竜一

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    Grant type:Competitive

    Grant amount:\2400000 ( Direct Cost: \2400000 )

    異なる領野間の機能的結合の特性と可塑性を解析した。解析対象は、41野(1次聴覚野)とその周辺の高次感覚野、20野(2次聴覚野)・36野(2次聴覚野)・18a野(2次視覚野)・39野(2次体性感覚野)である。スライス切断面を調整することで、41野といずれかの高次感覚野を含む脳スライスを調整、解析して次の4つの結果を得た。
    (1)領野間の機能的結合は、場所と方向により性質が異なる。
    (2)領野間の長距離機能的結合には、白質を介さず、灰白質内だけを通るものもある。
    (3)領野間の機能的結合には、反復刺激により増強するものがある。
    (4)領野間の機能的結合の可塑性には、固有の感受性期がある。

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  • Sound sequence discrimination learning dependent on cholinergic input to the auditory cortex

    Grant number:14580766

    2002 - 2003

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    KUDOH Masaharu, ULISHIDA Ryuichi

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    Grant amount:\3600000 ( Direct Cost: \3600000 )

    In rat auditory cortex (AC) slices, synaptic potentiation following heterosynaptic stimulation is affected by stimulus sequence used for induction. It was hypothesized that this sequence-dependent plasticity might be partly involved in the cellular mechanisms underlying sound sequence discrimination. Sequence dependence is abolished by muscarinic receptor antagonists. Therefore, dependence of sound sequence discrimination learning on cholinergic inputs to the rat AC was investigated. Water-deprived rats were trained to discriminate the sequences of two sound components and a licking behavior in response to one of two possible sequences was rewarded with water. Either rewarded (S+) or unrewarded (S-) sequence was presented randomly in a trial, which was repeated every one minute for 12 hours in 4 days. Percentage of trials in which rats licked the spout was calculated separately for S+ and S-, and test performance was estimated as the difference. Atropine (10 mg/kg, i.p.), an antagonist of muscarinic receptors, attenuated sound sequence discrimination learning, while methylatropine (10 mg/kg, i.p.), a muscarinic receptor antagonist unable to cross the blood-brain barrier, had no significant effect. Increased level of sound sequence discrimination during 4 days test session was maintained more than one week. Atropine had no effect on the acquired performance. Injection of the cholinergic immunotoxin 192IgG-saporin into the bilateral AC attenuated sound sequence discrimination learning, while discrimination between the two sound components was not affected. Linopirdine, a cognitive enhancer that inhibit M-type K^+ currents, restores the sequence dependence of synaptic potentiation in AC slices in the presence of atropine. In this study, sound sequence discrimination learning attenuated by 192IgG-saporin was also restored by linopirdine. These similarities between sequence dependent plasticity in the AC slices and sound sequence discrimination learning support the hypothesis that the former is involved in the cellular mechanisms underlying the latter.

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  • Application of endogenous autofluorescence signal for functional brain imaging

    Grant number:13358013

    2001 - 2003

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    SHIBUKI Katsuei, TANAKA Ryuichi, HISHIDA Ryuichi, KUDOH Masaharu, KOUUCHI Takeshi

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    Grant amount:\50830000 ( Direct Cost: \39100000 、 Indirect Cost:\11730000 )

    We developed a method of neural imaging using activity-dependent changes in green fluorescence of flavoproteins excited by blue light. We observed an increase in endogenous green fluorescence in response to electrical stimulation in the slices of the rat auditory cortex. The amplitude of the peak increase, which was observed 2-3 s after the initiation of the repetitive electrical stimulation, was as large as about 30% at room temperature. They were also not observed in the slices perfused with medium lacking calcium, glucose or oxygen. These data indicate that the green fluorescent responses are attributed to the fluorescence of flavoproteins involved in the energy metabolism in mitochondria. In anesthetized rats with urethane, we observed clear images of the green fluorescent changes on the exposed surface of the auditory cortex following sound stimuli. These fluorescent changes were observed without using averaging, since they were much larger than the optical noises caused by heartbeats or breathing. We also tried to investigate spatial pattern of correlation between spontaneous neural activites using fluctuations in flavoprotein fluorescence. In the normal somatosensory cortex covered with agar, positive correlation around a ROI was observed in the fluorescence signals after correction for breathing movements. Tetanic stimulation applied around the ROI increased the magnitude of the positive correlation around the ROI. This method was also used to visualize learning-induced changes of neural activities in the rat primary somatosensory cortex. A water-deprived rat was trained to discriminate the frequency (20 Hz or 40 z) of floor vibration in a Skinner box. After this discrimination learning was achieved in consecutive 3-5 days, the somatosensory neural responses to the rewarded frequency were larger than that in response to the unrewarded frequency in all of the rats tested. In mice, the transparent skull of mice allowed trans-cranial autofluorescence imaging of cortical activites.

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  • 大脳聴覚野シナプス可塑性による回路調節

    Grant number:12053224

    2000 - 2004

    System name:科学研究費助成事業

    Research category:特定領域研究

    Awarding organization:日本学術振興会

    澁木 克栄, 工藤 雅治, 菱田 竜一

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    Grant amount:\96800000 ( Direct Cost: \96800000 )

    マウスの頭蓋骨は透明度が高いので麻酔マウスの大脳皮質の光学的なイメージングを頭蓋骨を介して行うことができる。今年度はこの経頭蓋的フラビン蛋白蛍光イメージングを用いてマウス大脳皮質感覚野の可塑性を解析した。
    聴覚野では音刺激の高さによって特徴的な反応パターン(tonotopic map)が知られているが、これを確認した。次に特定の周波数(10キロヘルツ)の音に幼若期より曝したときの聴覚野可塑性について解析した。その結果、10キロヘルツの反応は有意に増強されるが、5キロや20キロヘルツに対する反応は必ずしも増強されなかった。音に曝す期間を色々変化させたが、その効果に特定の臨界期は認められなかった。また動物を防音室で飼育すると聴覚野の反応の振幅や持続時間が有意に小さくなった。明確な臨界期が認められないことは視床-皮質シナプスではなく、皮質内回路の変化を推定させる。この可能性について検討するため、様々な音環境で飼育した動物から皮質切片を作製し、上顆粒層に連発電気刺激を加えて、興奮パターンをフラビン蛋白蛍光法で解析した。その結果、皮質の深さ方向への興奮の伝搬が防音室で飼育したマウスでは有意に抑えられた。以上の結果は、発達期の音環境が聴覚野応答を可塑的に調節し、特に皮質の垂直方向の結合が活動依存的に調節されることを示している。
    さらに経頭蓋的フラビン蛋白蛍光イメージングをマウス視覚野活動の解析に利用したところ、視野に応じた皮質部位が応じ(retinotopic map)、また単眼の遮蔽により、遮蔽眼の応答が弱まることが判った。この時の可塑性は生後4週間前後に明確な臨界期が認められた。また体性感覚野では尾の切断に伴って、周辺の皮膚刺激に対する皮質応答部位(somatotopic map)が可塑的に改変されることが判った。

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  • Functional identification of synaptic plasticity in the rat auditory cortex

    Grant number:10480225

    1998 - 2000

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B).

    Awarding organization:Japan Society for the Promotion of Science

    SHIBUKI Katsuei, HISHIDA Ryuichi, KUDOH Masaharu

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    Grant amount:\12000000 ( Direct Cost: \12000000 )

    In this study, we investigated the physiological roles of synaptic plasticity in the rat auditory cortex. We studied long-term depression (LTD). The synaptic inputs to pyramidal neurons from the medial geniculate body exhibited LTD, which was sensitive to an antagonist of NMDA receptors. In contrast, LTD was sensitive to an antagonist of metabotropic glutamate receptors in the synapses between cortical pyramidal neurons. We further investigated sequence-dependent properties of long-term potentiation (LTP). The sequence-dependence was observed on the scale of seconds, so that LTP was observed only in the synapses stimulated earlier. The sequence-dependence of LTP was abolished in the presence of antagonists of muscarinic acetylcholine receptors. The importance of endogenous cholinergic was also shown in the sound-sequence discrimination ability of rats using behavioral analyses. These results suggest that the sequence-dependent LTP may have a role in temporal information processing in the auditory cortex. Finally, we investigated the properties between the auditory cortex and higher cortices. Primary sensory cortices can be activated by memory recall or imagery via feedback projections from higher cortices. We studied the properties of the cortical boundary between the auditory cortex and area 18a in rat cerebral slices. Activities in the auditory cortex were usually not elicited by the stimulation of area 18a. However, the whole auditory cortex was invaded by polysynaptic feedback activities triggered in area 18a, after area 18a and the auditory cortex were alternately stimulated several times. Our findings indicate that different cortical areas are quickly bound with feedback activities depending on previous activities.

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Teaching Experience (researchmap)

  • 医学研究実習

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  • 医科学研究法

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  • 生理学

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  • 解剖生理学実験

    Institution name:悠久山栄養調理専門学校

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  • 脳神経学

    Institution name:新潟医療技術専門学校

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  • 生理機能検査学

    Institution name:新潟医療技術専門学校

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