Updated on 2024/03/08

写真a

 
UEDA Shuhei
 
Organization
Research Institute of Environmental Medicine Division of Stress Recognition and Response Assistant Professor
Graduate School
Graduate School of Medicine
Title
Assistant Professor
External link

Degree 1

  1. 博士(生命科学) ( 2013.5   京都大学 ) 

Research Interests 9

  1. autism spectrum disorder

  2. schizophrenia

  3. psychiatric disorder

  4. neurodevelopmental disorder

  5. 包括脳ネットワーク

  6. molecular biology

  7. シナプス

  8. amygdala

  9. emotion

Research Areas 5

  1. Life Science / Molecular biology

  2. Life Science / Neuroscience-general

  3. Life Science / Function of nervous system

  4. Life Science / Pathophysiologic neuroscience

  5. Life Science / Animal physiological chemistry, physiology and behavioral biology

Research History 3

  1. Nagoya University   Research Institute of Environmental Medicine   Assistant Professor

    2017.4

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    Country:Japan

  2. Nagoya University   Research Institute of Environmental Medicine

    2016.4 - 2017.3

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    Country:Japan

  3. 京都大学大学院   医学研究科 メディカルイノベーションセンター   特定研究員

    2013.5 - 2016.3

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    Country:Japan

Education 2

  1. 京都大学大学院   生命科学研究科 博士課程

    2009.4 - 2013.3

  2. Kyoto University   Faculty of Pharmaceutical Science

    2002.4 - 2007.3

Professional Memberships 4

  1. THE JAPAN NEUROSCIENCE SOCIETY

  2. Society for Neuroscience

  3. Society for Neuroscience

  4. The Japanese Society of Neuropsychopharmacology

Committee Memberships 1

  1. Frontiers in Molecular Neuroscience   Review editor  

    2023.5   

 

Papers 11

  1. Experience-dependent changes in affective valence of taste in male mice. Reviewed International journal

    Shun Hamada†, Kaori Mikami†, Shuhei Ueda†, Masashi Nagase†, Takashi Nagashima, Mikiyasu Yamamoto, Haruhiko Bito, Sayaka Takemoto-Kimura, Toshihisa Ohtsuka, Ayako M Watabe

    Molecular brain   Vol. 16 ( 1 ) page: 28 - 28   2023.3

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

    Taste plays an essential role in the evaluation of food quality by detecting potential harm and benefit in what animals are about to eat and drink. While the affective valence of taste signals is supposed to be innately determined, taste preference can also be drastically modified by previous taste experiences of the animals. However, how the experience-dependent taste preference is developed and the neuronal mechanisms involved in this process are poorly understood. Here, we investigate the effects of prolonged exposure to umami and bitter tastants on taste preference using two-bottle tests in male mice. Prolonged umami exposure significantly enhanced umami preference with no changes in bitter preference, while prolonged bitter exposure significantly decreased bitter avoidance with no changes in umami preference. Because the central amygdala (CeA) is postulated as a critical node for the valence processing of sensory information including taste, we examined the responses of cells in the CeA to sweet, umami, and bitter tastants using in vivo calcium imaging. Interestingly, both protein kinase C delta (Prkcd)-positive and Somatostatin (Sst)-positive neurons in the CeA showed an umami response comparable to the bitter response, and no difference in cell type-specific activity patterns to different tastants was observed. Meanwhile, fluorescence in situ hybridization with c-Fos antisense probe revealed that a single umami experience significantly activates the CeA and several other gustatory-related nuclei, and especially CeA Sst-positive neurons were strongly activated. Intriguingly, after prolonged umami experience, umami tastant also significantly activates the CeA neurons, but the Prkcd-positive neurons instead of Sst-positive neurons were highly activated. These results suggest a relationship between amygdala activity and experience-dependent plasticity developed in taste preference and the involvement of the genetically defined neural populations in this process.

    DOI: 10.1186/s13041-023-01017-x

    Web of Science

    PubMed

  2. Author Correction: Remote control of neural function by X-ray-induced scintillation.

    Matsubara T, Yanagida T, Kawaguchi N, Nakano T, Yoshimoto J, Sezaki M, Takizawa H, Tsunoda SP, Horigane SI, Ueda S, Takemoto-Kimura S, Kandori H, Yamanaka A, Yamashita T

    Nature communications   Vol. 13 ( 1 ) page: 1950   2022.4

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

    DOI: 10.1038/s41467-022-29664-z

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

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

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    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

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    PubMed

  4. Remote control of neural function by X-ray-induced scintillation 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 - 1950   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>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 Gd<sub>3</sub>(Al,Ga)<sub>5</sub>O<sub>12</sub> (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

    Web of Science

    PubMed

    Other Link: http://www.nature.com/articles/s41467-021-24717-1

  5. 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

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    Authorship:Lead author   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

  6. From population to neuron: exploring common mediators for metabolic problems and mental illnesses Reviewed International coauthorship International journal

    Yoichiro Takayanagi, Koko Ishizuka, Thomas M. Laursen, Hiroshi Yukitake, Kun Yang, Nicola G. Cascella, Shuhei Ueda, Akiko Sumitomo, Zui Narita, Yasue Horiuchi, Minae Niwa, Akiko Taguchi, Morris F. White, William W. Eaton, Preben B. Mortensen, Takeshi Sakurai, Akira Sawa

    Molecular Psychiatry   Vol. 26 ( 8 ) page: 3931 - 3942   2020.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.

    DOI: 10.1038/s41380-020-00939-5

    PubMed

    Other Link: http://www.nature.com/articles/s41380-020-00939-5

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

    Horigane SI, Ozawa Y, Zhang J, Todoroki H, Miao P, Haijima A, Yanagawa Y, Ueda S, Nakamura S, Kakeyama M, Takemoto-Kimura S

    FEBS open bio     2020.6

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

    DOI: 10.1002/2211-5463.12924

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  8. Sequence of Molecular Events during the Maturation of the Developing Mouse Prefrontal Cortex. Reviewed International coauthorship International journal

    Ueda S, Niwa M, Hioki H, Sohn J, Kaneko T, Sawa A, Sakurai T

    Molecular neuropsychiatry   Vol. 1 ( 2 ) page: 94-104   2015.7

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

    DOI: 10.1159/000430095

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  9. Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation. Reviewed International journal

    Ueda S, Negishi M, Katoh H

    Molecular biology of the cell   Vol. 24 ( 10 ) page: 1602-13   2013.5

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

    DOI: 10.1091/mbc.E12-11-0782

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  10. Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. Reviewed International journal

    Hiramoto-Yamaki N, Takeuchi S, Ueda S, Harada K, Fujimoto S, Negishi M, Katoh H

    The Journal of cell biology   Vol. 190 ( 3 ) page: 461-77   2010.8

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

    DOI: 10.1083/jcb.201005141

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  11. Dock4 regulates dendritic development in hippocampal neurons. Reviewed International journal

    Ueda S, Fujimoto S, Hiramoto K, Negishi M, Katoh H

    Journal of neuroscience research   Vol. 86 ( 14 ) page: 3052-61   2008.11

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

    DOI: 10.1002/jnr.21763

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

  1. 摂食行動による情動神経回路の応答とストレスによる回路機構変容の解析

    Grant number:22K06483  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    上田 修平

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    Authorship:Principal investigator 

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

    摂食行動は、生命活動を行う上で必要なエネルギーや栄養素を摂取するための恒常的摂食に、味覚、嗅覚、視覚など外的刺激に誘発された情動変化による快楽的(もしくは情動的)摂食が相互作用して行われると考えられている。近年、摂食行動に異常を示す「摂食障害」が増加傾向にあり、その一因には社会的なストレスが関わっていると考えられていることから、本研究では、ストレスによる摂食調節神経回路機構破綻のメカニズム解明を行う。
    摂食行動は、生命活動を行う上で必要なエネルギーや栄養素を摂取するための恒常的摂食に、味覚、嗅覚、視覚など外的刺激に誘発された情動変化による快楽的(もしくは情動的)摂食が相互作用して行われると考えられている。近年、摂食行動に異常を示す「摂食障害」が増加傾向にあり、その一因には社会的なストレスが関わっていると考えられているが、ストレスがどのように神経回路機能に影響を与え、摂食行動の異常につながるかは未解明な部分が多い。本研究では、情動の中枢である扁桃体にフォーカスし、未だ不明な点が多い快楽的摂食調節における情動神経回路の役割、また、ストレスによりその神経回路機構がどのように破綻し摂食行動の異常につながるかを明らかにすることを目的としている。
    今年度は、扁桃体の中でも出力核にあたる扁桃体中心核において、扁桃体中心核に存在するPrkcd陽性細胞、Sst陽性細胞、Crh陽性細胞を対象にin vivoカルシウムイメージングを行い、各種細胞において情動変化をもたらす嗜好性の高い味質、忌避反応を引き起こす味質に応答する細胞が存在することを明らかにした。また摂食時に神経活動が亢進し、かつ嗜好性の高い味質物質にも応答する扁桃体中心核の特定の神経細胞について、その活動変化が、摂食行動にどのような影響を与えるかを明らかにするため、光遺伝学を用いた神経回路操作に着手した。次年度以降は摂食行動評価に用いる実験のセットアップの修正を行い、神経回路操作の影響の評価を行う。
    in vivoカルシウムイメージングによる神経活動計測のデータ取得、解析は順調に進んでおり、各種味質物質に対する応答について、論文にまとめ発表した。引き続き摂食時の神経活動変化についても解析を進める。また、光遺伝学による神経回路操作にも着手した。光遺伝学や薬理遺伝学による回路操作による摂食行動の変化を評価するため、実験のセットアップを一部見直す必要が出てきたが、大きな予定の変更は必要ないため、研究計画全体としては順調に進捗している。
    in vivoカルシウムイメージングによる神経活動計測については、引き続き取得したデータの解析を進めると同時に、ストレス負荷時の摂食、味質応答のデータ取得を行う。
    また、摂食行動評価に用いる実験のセットアップを整え、光遺伝学的操作や薬理遺伝学的操作にともなう摂食行動変化の解析を行う。

  2. Analysis of neural circuitry mechanism of the central amygdala in the control of feeding behavior

    Grant number:20K15929  2020.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Ueda Shuhei

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    Authorship:Principal investigator 

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

    It is thought that neural circuit of emotional regulation is involved in the control of feeding behavior, however its neural circuitry mechanism is still unclear. In this study, we focused on the central nucleus of the amygdala (CeA), which is the output nucleus of the emotional amygdala circuit, and recorded neuronal activity by using in vivo calcium imaging system about the three major cell-populations of the CeA. We analyzed neuronal activity responses in each cell population during feeding behavior, various tastant stimulations, and administration of gastrointestinal hormones, which are important factors of feeding behavior, and found that various feeding-related information are accumulated in the CeA and represented in a more complex way than previously thought.

 

Teaching Experience (Off-campus) 2

  1. Basic Training

    2018 Nagoya University)

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    Level:Graduate (liberal arts) 

  2. Special Lecture Tokuron "Advanced research on psychiatric disorder and drug development"

    2017.11 Nagoya University)

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    Level:Graduate (liberal arts)