Updated on 2022/03/15

写真a

 
HORIGANE Shin-ichiro
 
Organization
Research Institute of Environmental Medicine Division of Stress Recognition and Response Lecturer
Graduate School
Graduate School of Medicine
Title
Lecturer
Contact information
メールアドレス
External link

Degree 1

  1. 博士(医学) ( 2015.3   東京大学 ) 

Research Interests 7

  1. Neuronal circuit formation

  2. Voltage dependent Ca2+ channels (VDCCs)

  3. Neuronal migration

  4. Neurodevelopmental disorders

  5. Neuronal circuit formation

  6. Live imagign

  7. Calcium signaling

Research Areas 2

  1. Life Science / Neuroscience-general

  2. Life Science / Pathophysiologic neuroscience

Research History 4

  1. Nagoya University   Research Institute of Environmental Medicine   Lecturer

    2020.10

  2. Nagoya University   Research Institute of Environmental Medicine   Assistant Professor

    2016.3 - 2020.9

  3. 名古屋大学環境医学研究所 研究機関研究員

    2015.9 - 2016.2

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    Country:Japan

  4. 東京大学大学院医学系研究科 神経生化学分野 特任研究員

    2015.4 - 2015.8

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    Country:Japan

Education 3

  1. The University of Tokyo   Graduate School, Division of Medical Sciences

    2011.4 - 2015.3

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    Country: Japan

  2. The University of Tokyo

    2009.4 - 2011.3

  3. University of Tsukuba   Second Cluster of College

    2005.4 - 2009.3

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    Country: Japan

Professional Memberships 3

  1. The Japanese Society for Neurochemistry

  2. 日本神経科学会

  3. Society for Neuroscience

 

Papers 13

  1. Identification of ultra-rare disruptive variants in voltage-gated calcium channel-encoding genes in Japanese samples of schizophrenia and autism spectrum disorder. International journal

    Chenyao Wang*, Shin-ichiro Horigane*, Minoru Wakamori*, Shuhei Ueda, Takeshi Kawabata, Hajime Fujii, Itaru Kushima, Hiroki Kimura, Kanako Ishizuka, Yukako Nakamura, Yoshimi Iwayama, Masashi Ikeda, Nakao Iwata, Takashi Okada, Branko Aleksic, Daisuke Mori, Takashi Yoshida, Haruhiko Bito, Takeo Yoshikawa, Sayaka Takemoto-Kimura, Norio Ozaki, (*co-first)

    Translational psychiatry   Vol. 12 ( 1 ) page: 84 - 84   2022.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Several large-scale whole-exome sequencing studies in patients with schizophrenia (SCZ) and autism spectrum disorder (ASD) have identified rare variants with modest or strong effect size as genetic risk factors. Dysregulation of cellular calcium homeostasis might be involved in SCZ/ASD pathogenesis, and genes encoding L-type voltage-gated calcium channel (VGCC) subunits Cav1.1 (CACNA1S), Cav1.2 (CACNA1C), Cav1.3 (CACNA1D), and T-type VGCC subunit Cav3.3 (CACNA1I) recently were identified as risk loci for psychiatric disorders. We performed a screening study, using the Ion Torrent Personal Genome Machine (PGM), of exon regions of these four candidate genes (CACNA1C, CACNA1D, CACNA1S, CACNA1I) in 370 Japanese patients with SCZ and 192 with ASD. Variant filtering was applied to identify biologically relevant mutations that were not registered in the dbSNP database or that have a minor allele frequency of less than 1% in East-Asian samples from databases; and are potentially disruptive, including nonsense, frameshift, canonical splicing site single nucleotide variants (SNVs), and non-synonymous SNVs predicted as damaging by five different in silico analyses. Each of these filtered mutations were confirmed by Sanger sequencing. If parental samples were available, segregation analysis was employed for measuring the inheritance pattern. Using our filter, we discovered one nonsense SNV (p.C1451* in CACNA1D), one de novo SNV (p.A36V in CACNA1C), one rare short deletion (p.E1675del in CACNA1D), and 14 NSstrict SNVs (non-synonymous SNV predicted as damaging by all of five in silico analyses). Neither p.A36V in CACNA1C nor p.C1451* in CACNA1D were found in 1871 SCZ cases, 380 ASD cases, or 1916 healthy controls in the independent sample set, suggesting that these SNVs might be ultra-rare SNVs in the Japanese population. The neuronal splicing isoform of Cav1.2 with the p.A36V mutation, discovered in the present study, showed reduced Ca2+-dependent inhibition, resulting in excessive Ca2+ entry through the mutant channel. These results suggested that this de novo SNV in CACNA1C might predispose to SCZ by affecting Ca2+ homeostasis. Thus, our analysis successfully identified several ultra-rare and potentially disruptive gene variants, lending partial support to the hypothesis that VGCC-encoding genes may contribute to the risk of SCZ/ASD.

    DOI: 10.1038/s41398-022-01851-y

    PubMed

  2. A Flp-dependent G-CaMP9a transgenic mouse for neuronal imaging in vivo

    Masayuki Sakamoto, Masatoshi Inoue, Atsuya Takeuchi, Shigetaka Kobari, Tatsushi Yokoyama, Shin-ichiro Horigane, Sayaka Takemoto-Kimura, Manabu Abe, Kenji Sakimura, Masanobu Kano, Kazuo Kitamura, Hajime Fujii, Haruhiko Bito

    Cell Reports Methods     page: 100168 - 100168   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.crmeth.2022.100168

  3. Distinctive Regulation of Emotional Behaviors and Fear-Related Gene Expression Responses in Two Extended Amygdala Subnuclei With Similar Molecular Profiles. Reviewed International journal

    Shuhei Ueda, Masahito Hosokawa, Koji Arikawa, Kiyofumi Takahashi, Mao Fujiwara, Manami Kakita, Taro Fukada, Hiroaki Koyama, Shin-Ichiro Horigane, Keiichi Itoi, Masaki Kakeyama, Hiroko Matsunaga, Haruko Takeyama, Haruhiko Bito, Sayaka Takemoto-Kimura

    Frontiers in molecular neuroscience   Vol. 14   page: 741895 - 741895   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    The central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST) are the two major nuclei of the central extended amygdala that plays essential roles in threat processing, responsible for emotional states such as fear and anxiety. While some studies suggested functional differences between these nuclei, others showed anatomical and neurochemical similarities. Despite their complex subnuclear organization, subnuclei-specific functional impact on behavior and their underlying molecular profiles remain obscure. We here constitutively inhibited neurotransmission of protein kinase C-δ-positive (PKCδ+) neurons-a major cell type of the lateral subdivision of the CeA (CeL) and the oval nucleus of the BNST (BNSTov)-and found striking subnuclei-specific effects on fear- and anxiety-related behaviors, respectively. To obtain molecular clues for this dissociation, we conducted RNA sequencing in subnuclei-targeted micropunch samples. The CeL and the BNSTov displayed similar gene expression profiles at the basal level; however, both displayed differential gene expression when animals were exposed to fear-related stimuli, with a more robust expression change in the CeL. These findings provide novel insights into the molecular makeup and differential engagement of distinct subnuclei of the extended amygdala, critical for regulation of threat processing.

    DOI: 10.3389/fnmol.2021.741895

    Web of Science

    PubMed

  4. Remote control of neural function by X-ray-induced scintillation. Reviewed International journal

    Takanori Matsubara, Takayuki Yanagida, Noriaki Kawaguchi, Takashi Nakano, Junichiro Yoshimoto, Maiko Sezaki, Hitoshi Takizawa, Satoshi P Tsunoda, Shin-Ichiro Horigane, Shuhei Ueda, Sayaka Takemoto-Kimura, Hideki Kandori, Akihiro Yamanaka, Takayuki Yamashita

    Nature communications   Vol. 12 ( 1 ) page: 4478 - 4478   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), can effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively. Using injectable Ce:GAGG microparticles, we successfully activated and inhibited midbrain dopamine neurons in freely moving mice by X-ray irradiation, producing bidirectional modulation of place preference behavior. Ce:GAGG microparticles are non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level is sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables minimally invasive, wireless control of cellular functions at any tissue depth in living animals, expanding X-ray applications to functional studies of biology and medicine.

    DOI: 10.1038/s41467-021-24717-1

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  5. A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development. Reviewed International journal

    Shin-Ichiro Horigane, Yukihiro Ozawa, Jun Zhang, Hiroe Todoroki, Pan Miao, Asahi Haijima, Yuchio Yanagawa, Shuhei Ueda, Shigeo Nakamura, Masaki Kakeyama, Sayaka Takemoto-Kimura

    FEBS open bio   Vol. 10 ( 8 ) page: 1436 - 1446   2020.8

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Multiple genetic factors related to autism spectrum disorder (ASD) have been identified, but the biological mechanisms remain obscure. Timothy syndrome (TS), associated with syndromic ASD, is caused by a gain-of-function mutation, G406R, in the pore-forming subunit of L-type Ca2+ channels, Cav 1.2. In this study, a mouse model of TS, TS2-neo, was used to enhance behavioral phenotyping and to identify developmental anomalies in inhibitory neurons. Using the IntelliCage, which enables sequential behavioral tasks without human handling and mouse isolation stress, high-social competitive dominance was observed in TS2-neo mice. Furthermore, histological analysis demonstrated inhibitory neuronal abnormalities in the neocortex, including an excess of smaller-sized inhibitory presynaptic terminals in the somatosensory cortex of young adolescent mice and higher numbers of migrating inhibitory neurons from the medial ganglionic eminence during embryonic development. In contrast, no obvious changes in excitatory synaptic terminals were found. These novel neural abnormalities in inhibitory neurons of TS2-neo mice may result in a disturbed excitatory/inhibitory (E/I) balance, a key feature underlying ASD.

    DOI: 10.1002/2211-5463.12924

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    PubMed

  6. Development of an L-type Ca2+ channel-dependent Ca2+ transient during the radial migration of cortical excitatory neurons. Reviewed International journal

    Shin-Ichiro Horigane, Shun Hamada, Satoshi Kamijo, Hirokazu Yamada, Miwako Yamasaki, Masahiko Watanabe, Haruhiko Bito, Toshihisa Ohtsuka, Sayaka Takemoto-Kimura

    Neuroscience research     2020.6

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Increasing evidence has shown that voltage-gated L-type Ca2+ channels (LTCCs) are crucial for neurodevelopmental events, including neuronal differentiation/migration and neurite morphogenesis/extension. However, the time course of their functional maturation during the development of excitatory neurons remains unknown. Using a combination of fluorescence in situ hybridization and in utero electroporation-based labeling, we found that the transcripts of Cacna1c and Cacna1d, which encode the LTCC pore-forming subunits, were upregulated in the intermediate zone (IZ) during radial migration. Ca2+ imaging using GCaMP6s in acute brain slices showed spontaneous Ca2+ transients in migrating neurons throughout the IZ. Neurons in the IZ upper layer, especially in the multipolar-to-bipolar transition layer (TL), exhibited more frequent Ca2+ transients than adjacent layers and responded to FPL64176, a potent activator of LTCC. Consistently, nimodipine, an LTCC blocker, inhibited spontaneous Ca2+ transients in neurons in the TL. Collectively, we showed a hitherto unknown increased prevalence of LTCC-dependent Ca2+ transients in the TL of the IZ upper layer during the radial migration of excitatory neurons, which could be essential for the regulation of Ca2+-dependent neurodevelopmental processes.

    DOI: 10.1016/j.neures.2020.06.003

    PubMed

  7. Rational Engineering of XCaMPs, a Multicolor GECI Suite for In Vivo Imaging of Complex Brain Circuit Dynamics. Reviewed International journal

    Masatoshi Inoue, Atsuya Takeuchi, Satoshi Manita, Shin-Ichiro Horigane, Masayuki Sakamoto, Ryosuke Kawakami, Kazushi Yamaguchi, Kouhei Otomo, Hiroyuki Yokoyama, Ryang Kim, Tatsushi Yokoyama, Sayaka Takemoto-Kimura, Manabu Abe, Michiko Okamura, Yayoi Kondo, Sean Quirin, Charu Ramakrishnan, Takeshi Imamura, Kenji Sakimura, Tomomi Nemoto, Masanobu Kano, Hajime Fujii, Karl Deisseroth, Kazuo Kitamura, Haruhiko Bito

    Cell   Vol. 177 ( 5 ) page: 1346 - 1360   2019.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    To decipher dynamic brain information processing, current genetically encoded calcium indicators (GECIs) are limited in single action potential (AP) detection speed, combinatorial spectral compatibility, and two-photon imaging depth. To address this, here, we rationally engineered a next-generation quadricolor GECI suite, XCaMPs. Single AP detection was achieved within 3-10 ms of spike onset, enabling measurements of fast-spike trains in parvalbumin (PV)-positive interneurons in the barrel cortex in vivo and recording three distinct (two inhibitory and one excitatory) ensembles during pre-motion activity in freely moving mice. In vivo paired recording of pre- and postsynaptic firing revealed spatiotemporal constraints of dendritic inhibition in layer 1 in vivo, between axons of somatostatin (SST)-positive interneurons and apical tufts dendrites of excitatory pyramidal neurons. Finally, non-invasive, subcortical imaging using red XCaMP-R uncovered somatosensation-evoked persistent activity in hippocampal CA1 neurons. Thus, the XCaMPs offer a critical enhancement of solution space in studies of complex neuronal circuit dynamics. VIDEO ABSTRACT.

    DOI: 10.1016/j.cell.2019.04.007

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    PubMed

  8. Calcium signalling: a key regulator of neuronal migration. Invited Reviewed

    Horigane SI, Ozawa Y, Yamada H, Takemoto-Kimura S

    Journal of biochemistry   Vol. 165 ( 5 ) page: 401-409   2019.5

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/jb/mvz012

    PubMed

  9. A Critical Neurodevelopmental Role for L-Type Voltage-Gated Calcium Channels in Neurite Extension and Radial Migration Reviewed

    Kamijo Satoshi, Ishii Yuichiro, Horigane Shin-ichiro, Suzuki Kanzo, Ohkura Masamichi, Nakai Junichi, Fujii Hajime, Takemoto-Kimura Sayaka, Bito Haruhiko

    JOURNAL OF NEUROSCIENCE   Vol. 38 ( 24 ) page: 5551-5566   2018.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1523/JNEUROSCI.2357-17.2018

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    PubMed

  10. Calmodulin kinases: essential regulators in health and disease Invited Reviewed

    Takemoto-Kimura Sayaka, Suzuki Kanzo, Horigane Shin-Ichiro, Kamijo Satoshi, Inoue Masatoshi, Sakamoto Masayuki, Fujii Hajime, Bito Haruhiko

    JOURNAL OF NEUROCHEMISTRY   Vol. 141 ( 6 ) page: 808-818   2017.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/jnc.14020

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    PubMed

  11. Exploring the function of calcium-dependent phosphorylation in neuronal morphogenesis and circuit formation. Reviewed International journal

    Takemoto-Kimura S, Horigane S

    Jpn. J. Neuropsychopharmacol   Vol. 37   page: 163 - 167   2017

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  12. Facilitation of axon outgrowth via a Wnt5a-CaMKK-CaMKIα pathway during neuronal polarization Reviewed

    Horigane S, Ageta-Ishihara N, Kamijo S, Fujii H, Okamura M, Kinoshita M, Takemoto-Kimura S, Bito H

    Molecular Brain     2016.1

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s13041-016-0189-3

  13. Rational design of a high-affinity, fast, red calcium indicator R-CaMP2 Reviewed

    Inoue M, Takeuchi A, Horigane S, Ohkura M, Gengyo-Ando K, Fujii H, Kamijo S, Takemoto-Kimura S, Kano M, Nakai J, Kitamura K, Bito H

    Nature Methods     2014.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nmeth.3185

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Books 1

  1. 細胞内Ca2+シグナリングを介した発生期神経細胞移動の制御

    堀金慎一郎( Role: Joint author)

    日本生物学的精神医学会機関誌  2019.3 

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    Language:Japanese

Presentations 5

  1. Deciphering Ca2+ signaling during radial migration of immature cortical neurons.

    HORIGANE Shin-ichiro

    The 60th Annual Meeting of the Japanese Society for Neurochemistry (JSN)  2017.9.7 

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    Language:English   Presentation type:Oral presentation (general)  

  2. Deciphering a calcium-regulated pathway that controls radial migration of im mature cortical neurons

    HORIGANE Shin-ichiro

    The 41st Annual Meeting of Japan Neuroscience Society  2018.7.26 

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    Language:English   Presentation type:Oral presentation (general)  

  3. Deciphering a calcium-regulated pathway that controls radial migration of cortical neurons via the excitation-coupled morphological change

    HORIGANE Shin-ichiro

    Neuro 2019  2019.7.25 

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    Language:English   Presentation type:Oral presentation (general)  

  4. Calcium transients control a morphogenetic cycle underlying neuronal migratory movement International conference

    HORIGANE Shin-ichiro

    2019.10.23 

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    Language:English   Presentation type:Oral presentation (general)  

  5. Deciphering a calcium-regulated pathway that controls radial migration of im mature cortical neurons Invited

    HORIGANE Shin-ichiro

    The Joint Congress of the 40th Annual Meeting of Japanese Society of Biological Psychiatry and the 61st Annual Meeting of the Japanese Society for Neurochemistry  2018.9.7 

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    Language:English   Presentation type:Oral presentation (general)  

Research Project for Joint Research, Competitive Funding, etc. 2

  1. 自閉スペクトラム症の病態理解にむけたカルシウムシグナリング破綻を原因とする神経回路形成障害の解明

    2019.11 - 2021.11

    武田科学振興財団  研究助成 

    堀金慎一郎

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2000000

  2. 新規病態モデルを用いた多角的解析による発達障害の神経回路病態解明

    2019.9 - 2021.9

    豊秋奨学会  研究費助成 

    堀金慎一郎

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2500000

KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. 自閉スペクトラム症に合併する運動機能障害に対する新たな治療戦略の開発

    2022 - 2023

    Shin-ichiro Horigane

  2. カルシウムシグナリング破綻に着目した自閉スペクトラム症における神経回路病態の解明

    Grant number:20K16490  2020.4 - 2022.3

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    堀金 慎一郎

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    カルシウムイオンは、神経回路形成や神経可塑性など多様な細胞イベントを制御する。近年、カルシウムシグナリング破綻と精神障害との関係が注目されるが、両者の因果関係については多くが未解明である。我々はこれまでに、自閉スペクトラム症(ASD)患者から同定された変異型のL型カルシウムチャネルを発現するマウス系統を作出した。本研究では、同モデルマウスを用いることで、カルシウムシグナリング破綻とASD病態との関係を検討する。また更に、同マウス系統への介入操作によるASD病態の回復を検討する。すなわち本計画では、カルシウムシグナリング破綻に着目したASD病態の解明および治療法の探索を目的とする。

Industrial property rights 2

  1. Timothy症候群のモデル動物

    竹本さやか, 堀金慎一郎, 阿部学, 小澤享弘

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    Applicant:名古屋大学

    Application no:特願2021-108698  Date applied:2021.6

  2. 細胞内カルシウム動態評価系

    竹本さやか, 堀金慎一郎, 尾崎紀夫, 有岡祐子

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    Date applied:2018.3

    Announcement no:2019-154272  Date announced:2019.9

    Country of applicant:Domestic   Country of acquisition:Domestic