高田　則雄 （タカタ　ノリオ）

Takata, Norio

写真a

所属（所属キャンパス）

医学部 先端医科学研究所（脳科学） （信濃町）

職名

専任講師

HP
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経歴 【 表示 ／ 非表示 】

  • 1999年04月
    -
    2002年03月

    学術振興会特別研究員（DC1）

  • 2002年04月
    -
    2005年03月

    東京大学大学院総合文化研究科広域科学専攻生命環境科学系研究員

  • 2005年04月
    -
    2012年05月

    独立行政法人理化学研究所脳科学総合研究センター研究員

  • 2012年06月
    -
    継続中

    慶應義塾大学医学部精神・神経科学教室情動の制御と治療寄附講座

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学歴 【 表示 ／ 非表示 】

  • 1997年03月

    東京工業大学, 理学部, 物理学科

    大学, 卒業

  • 1997年04月
    -
    1999年03月

    東京大学, 総合文化研究科, 広域科学専攻

    大学院, 修了, 修士

  • 1999年04月
    -
    2002年03月

    東京大学, 総合文化研究科, 広域科学専攻

    大学院, 修了, 博士

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論文 【 表示 ／ 非表示 】

  • Flexible annotation atlas of the mouse brain: combining and dividing brain structures of the Allen Brain Atlas while maintaining anatomical hierarchy

    Takata N., Sato N., Komaki Y., Okano H., Tanaka K.F.

    Scientific Reports （Scientific Reports）  11 （ 1 ）  2021年12月

    　概要を見る

    A brain atlas is necessary for analyzing structure and function in neuroimaging research. Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researcher’s necessity, leading to inconsistent ROIs among studies. One reason for such a situation is the fact that earlier AVs were fixed, i.e. combination and division of nodes were not implemented. This report presents a pipeline for constructing a flexible annotation atlas (FAA) of the mouse brain by leveraging public resources of the Allen Institute for Brain Science on brain structure, gene expression, and axonal projection. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. Four FAAs with total node count of 4, 101, 866, and 1381 were demonstrated. Unique characteristics of FAA realized analysis of resting-state functional connectivity (FC) across the anatomical hierarchy and among cortical layers, which were thin but large brain structures. FAA can improve the consistency of whole brain ROI definition among laboratories by fulfilling various requests from researchers with its flexibility and reproducibility.

  • Chronic social defeat stress impairs goal-directed behavior through dysregulation of ventral hippocampal activity in male mice

    Yoshida K., Drew M.R., Kono A., Mimura M., Takata N., Tanaka K.F.

    Neuropsychopharmacology （Neuropsychopharmacology）  46 （ 9 ） 1606 - 1616 2021年08月

    ISSN  0893133X

    　概要を見る

    Chronic stress is a risk factor for a variety of psychiatric disorders, including depression. Although impairments to motivated behavior are a major symptom of clinical depression, little is known about the circuit mechanisms through which stress impairs motivation. Furthermore, research in animal models for depression has focused on impairments to hedonic aspects of motivation, whereas patient studies suggest that impairments to appetitive, goal-directed motivation contribute significantly to motivational impairments in depression. Here, we characterized goal-directed motivation in repeated social defeat stress (R-SDS), a well-established mouse model for depression in male mice. R-SDS impaired the ability to sustain and complete goal-directed behavior in a food-seeking operant lever-press task. Furthermore, stress-exposed mice segregated into susceptible and resilient subpopulations. Interestingly, susceptibility to stress-induced motivational impairments was unrelated to stress-induced social withdrawal, another prominent effect of R-SDS in mouse models. Based on evidence that ventral hippocampus (vHP) modulates sustainment of goal-directed behavior, we monitored vHP activity during the task using fiber photometry. Successful task completion was associated with suppression of ventral hippocampal neural activity. This suppression was diminished after R-SDS in stress-susceptible but not stress-resilient mice. The serotonin selective reuptake inhibitor (SSRI) escitalopram and ketamine both normalized vHP activity during the task and restored motivated behavior. Furthermore, optogenetic vHP inhibition was sufficient to restore motivated behavior after stress. These results identify vHP hyperactivity as a circuit mechanism of stress-induced impairments to goal-directed behavior and a putative biomarker that is sensitive to antidepressant treatments and that differentiates susceptible and resilient individuals.

  • Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice

    Abe Y., Kwon S., Oishi M., Unekawa M., Takata N., Seki F., Koyama R., Abe M., Sakimura K., Masamoto K., Tomita Y., Okano H., Mushiake H., Tanaka K.F.

    Cell Reports （Cell Reports）  36 （ 4 ）  2021年07月

    　概要を見る

    An artificial tool for manipulating local cerebral blood flow (CBF) is necessary for understanding how CBF controls brain function. Here, we generate vascular optogenetic tools whereby smooth muscle cells and endothelial cells express optical actuators in the brain. The illumination of channelrhodopsin-2 (ChR2)-expressing mice induces a local reduction in CBF. Photoactivated adenylyl cyclase (PAC) is an optical protein that increases intracellular cyclic adenosine monophosphate (cAMP), and the illumination of PAC-expressing mice induces a local increase in CBF. We target the ventral striatum, determine the temporal kinetics of CBF change, and optimize the illumination intensity to confine the effects to the ventral striatum. We demonstrate the utility of this vascular optogenetic manipulation in freely and adaptively behaving mice and validate the task- and actuator-dependent behavioral readouts. The development of vascular optogenetic animal models will help accelerate research linking vasculature, circuits, and behavior to health and disease.

  • Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep–wake states

    Natsubori A., Tsunematsu T., Karashima A., Imamura H., Kabe N., Trevisiol A., Hirrlinger J., Kodama T., Sanagi T., Masamoto K., Takata N., Nave K.A., Matsui K., Tanaka K.F., Honda M.

    Communications Biology （Communications Biology）  3 （ 1 ）  2020年12月

    　概要を見る

    Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons.

  • Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain

    Kawamura A., Abe Y., Seki F., Katayama Y., Nishiyama M., Takata N., Tanaka K.F., Okano H., Nakayama K.I.

    Molecular Brain （Molecular Brain）  13 （ 1 ）  2020年12月

    　概要を見る

    CHD8 encodes a chromatin-remodeling factor and is one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Although we have recently shown that mice heterozygous for Chd8 mutation manifest myelination defects and ASD-like behaviors, the detailed mechanisms underlying ASD pathogenesis have remained unclear. Here we performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) in oligodendrocyte lineage-specific Chd8 heterozygous mutant mice. DTI revealed that ablation of Chd8 specifically in oligodendrocytes of mice was associated with microstructural changes of specific brain regions including the cortex and striatum. The extent of these changes in white matter including the corpus callosum and fornix was correlated with total contact time in the reciprocal social interaction test. Analysis with rsfMRI revealed changes in functional brain connectivity in the mutant mice, and the extent of such changes in the cortex, hippocampus, and amygdala was also correlated with the change in social interaction. Our results thus suggest that changes in brain microstructure and functional connectivity induced by oligodendrocyte dysfunction might underlie altered social interaction in mice with oligodendrocyte-specific CHD8 haploinsufficiency.

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総説・解説等 【 表示 ／ 非表示 】

  • 光遺伝学とマウスfMRIとを融合させた脳領域間作用の解析

    高田 則雄

    細胞工学 （秀潤社）  33 （ 3 ） 281 - 285 2014年03月

    記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 睡眠覚醒に伴って変化する全脳活動パターンの特定と視床網様核による制御機構の解明

    2024年04月
    -
    2028年03月

    高田 則雄, 基盤研究(B), 補助金,  研究代表者

  • 覚醒剤急性中毒によって異常行動が発現する病態生理機構のマルチスケール解析

    2021年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 高田 則雄, 新学術領域研究（研究領域提案型）, 補助金,  研究代表者

  • 視床網様核の新規振動活動が感覚刺激時の神経応答ゆらぎに及ぼす因果的役割の解明

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 高田　則雄, 基盤研究（Ｃ）, 補助金,  研究代表者

  • 睡眠覚醒リズムに依存する脳領域間の機能的結合強度を視床網様核が制御する機構の解明

    2018年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 高田　則雄, 新学術領域研究(研究領域提案型), 補助金,  研究代表者

  • マウス全脳に対応する脳領域名の総数を1から860まで可変な標準脳の構築

    2016年04月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 高田　則雄, 基盤研究(C), 補助金,  研究代表者

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担当授業科目 【 表示 ／ 非表示 】

  • ＭＣＢ

    2024年度

  • ＭＣＢ

    2023年度

  • 生理学Ⅰ

    2022年度

  • 生理学Ⅰ

    2021年度

  • 生理学Ⅰ

    2020年度

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担当経験のある授業科目 【 表示 ／ 非表示 】

  • 自主学習

    慶應義塾

    2015年04月
    -
    2016年03月

  • 生理学（Ⅰ）実習

    慶應義塾

    2015年04月
    -
    2016年03月

  • 自主学習

    慶應義塾

    2014年04月
    -
    2015年03月

  • 生理学（Ⅰ）実習

    慶應義塾

    2014年04月
    -
    2015年03月

  • 自主学習

    慶應義塾

    2013年04月
    -
    2014年03月

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