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Electrophysiological and photometrical analysis of limbic neuronal activity in Alzheimer's mice

Research Project

Project/Area Number 17H02223
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Brain biometrics
Research InstitutionKanazawa Medical University

Principal Investigator

KATO Nobuo  金沢医科大学, 医学部, 教授 (10152729)

Co-Investigator(Kenkyū-buntansha) 大森 治紀  京都大学, 医学研究科, 名誉教授 (30126015)
小野 宗範  金沢医科大学, 医学部, 准教授 (30422942)
山本 亮  金沢医科大学, 医学部, 講師 (30447974)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Keywordsアルツハイマー病 / モデルマウス / 測光パッチ電極 / 細胞内カルシウム / シータ波 / 海馬脳波 / 認知行動テスト / Alzheimer's disease / Hippocampus / Photometry / Field potential / Theta wave / Awake / Model mice / Intracellular calcium / 認知症 / マウスモデル / シナプス可塑性 / 認知情報 / 病態脳科学 / 高次脳機能計測 / 神経可塑性 / 分子・細胞生理学
Outline of Final Research Achievements

The photometric patch electrode system, originally developed for recording from the avian auditory system, has been applied to the rodent hippocampus and fine-tuned. Instead of the original auditory stimulation, spontaneous walking on a treadmill that elicits theta waves was used to evoke electrical signals of neuronal origin in the hippocampus. We discovered that the high-frequency gamma component in the theta wave accompanies a large calcium transient in wild-type but not Alzheimer’s model mice. Cognitive performance measured with the Morris water maze is correlated well with the high frequency theta power at 150-250 Hz. The density of hippocampal excitatory synapses, as measured by EM, was revealed to correlate inversely with the cognitive score. An exuberance of unsynchronized excitatory synaptic volley was implicated for a basis of cognitive impairment.

Academic Significance and Societal Importance of the Research Achievements

海馬の属する辺縁系など脳の深部において、動物行動に起因する脳波活動など脳由来の集合的神経原性電気活動とそれに随伴する集合的細胞内カルシウム増加を同時記録した例は本研究が世界初である。脳の深部に至るほどカルシウム測光は困難になるが、本研究では測光パッチ電極法により克服した。アルツハイマー病モデルにおいて、海馬脳波の高周波成分が認知機能と相関することを見出した。認知異常の背景としてアルツハイマーモデルマウスにおける興奮性シナプスの形成過剰と非同期な細胞内カルシウム流入が示唆され、治療法開発への端緒を得た。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Int'l Joint Research] Huazhong Univ. Science and Technology(中国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Remodeling of projections from ventral hippocampus to prefrontal cortex in Alzheimer's mice2020

    • Author(s)
      Xu Feng、Ono Munenori、Ito Tetsufumi、Uchiumi Osamu、Wang Furong、Zhang Yu、Sun Peng、Zhang Qing、Yamaki Sachiko、Yamamoto Ryo、Kato Nobuo
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 7 Pages: 1486-1498

    • DOI

      10.1002/cne.25032

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Acoustic trauma induced the alteration of the activity balance of excitatory and inhibitory neurons in the inferior colliculus of mice2020

    • Author(s)
      Ma Lanlan、Ono Munenori、Qin Ling、Kato Nobuo
    • Journal Title

      Hearing Research

      Volume: 391 Pages: 107957-107957

    • DOI

      10.1016/j.heares.2020.107957

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Combinational Approach of Genetic SHP-1 Suppression and Voluntary Exercise Promotes Corticospinal Tract Sprouting and Motor Recovery Following Brain Injury2020

    • Author(s)
      Tanaka Takashi、Ito Tetsufumi、Sumizono Megumi、Ono Munenori、Kato Nobuo、Honma Satoru、Ueno Masaki
    • Journal Title

      Neurorehabilitation and Neural Repair

      Volume: 34 Issue: 6 Pages: 558-570

    • DOI

      10.1177/1545968320921827

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of autoantibodies in autoimmune encephalitis in relation to antigen localization: a non-systematic review2020

    • Author(s)
      Keiko Tanaka, Meiko Kawamura, Kenji Sakimura, Nobuo Kato.
    • Journal Title

      Int J Mol Sci21

      Volume: 21 Issue: 14 Pages: 1-15

    • DOI

      10.3390/ijms21144941

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and Characterization of Mammalian Otic Progenitor Cells that Can Differentiate into Both Sensory Epithelial and Neuronal Cell Lineages2020

    • Author(s)
      Kojima Ken、Nishida Akiko T.、Tashiro Kei、Hirota Kiichi、Nishio Takeshi、Murata Miyahiko、Kato Nobuo、Kawaguchi Saburo、Zine Azel、Ito Juichi、Water Thomas R.
    • Journal Title

      The Anatomical Record

      Volume: 303 Issue: 3 Pages: 451-460

    • DOI

      10.1002/ar.24335

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serotonergic control of GABAergic inhibition in the lateral amygdala2020

    • Author(s)
      Yamamoto Ryo、Furuyama Takafumi、Sugai Tokio、Ono Munenori、Pare Denis、Kato Nobuo
    • Journal Title

      Journal of Neurophysiology

      Volume: 123 Issue: 2 Pages: 670-681

    • DOI

      10.1152/jn.00500.2019

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 24S-hydroxycholesterol alters activity of large-conductance Ca2+-dependent K+ (slo1 BK) channel through intercalation into plasma membrane2019

    • Author(s)
      Tajima Nobuyoshi、Xiaoyan Liu、Taniguchi Makoto、Kato Nobuo
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 1864 Issue: 10 Pages: 1525-1535

    • DOI

      10.1016/j.bbalip.2019.05.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The enantiomer pair of 24S‐ and 24R‐hydroxycholesterol differentially alter activity of large‐conductance Ca 2+ ‐dependent K + (slo1 BK) channel2019

    • Author(s)
      Liu Xiaoyan、Tajima Nobuyoshi、Taniguchi Makoto、Kato Nobuo
    • Journal Title

      Chirality

      Volume: 32 Issue: 2 Pages: 223-230

    • DOI

      10.1002/chir.23157

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Optogenetics identification of neuronal type in awake mice with a glass optrode.2018

    • Author(s)
      Ono M, Muramoto S, Ma L, Kato N.
    • Journal Title

      Journal of Visualized Experiments

      Volume: 136 Issue: 136 Pages: 1-7

    • DOI

      10.3791/57781

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Neural Circuits in the Mammalian Auditory Midbrain.2018

    • Author(s)
      Ono M, Ito T.
    • Journal Title

      Journal of Experimental neuroscience

      Volume: 12 Pages: 1-11

    • DOI

      10.1177/1179069518818230

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 電気生理で覗くアルツハイマーうつ連関2021

    • Author(s)
      加藤伸郎
    • Organizer
      第197回北陸精神神経学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Simultaneous in vivo recording of the electrical activities and the signal of fluorescent calcium indicator in the hippocampus of Altzheimer's mouse model.2020

    • Author(s)
      小野宗範
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Aberrant balance between the excitatory and inhibitory neuronal activities in the inferior colliculus after the cochlear insults.2019

    • Author(s)
      馬蘭蘭, 小野宗範, 加藤伸郎
    • Organizer
      第42回神経科学学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Simultaneous in vivo recording of the electrical activities and the signal of fluorescent calcium indicator in the hippocampus of Altzheimer's mouse model.2019

    • Author(s)
      小野宗範, 大森治紀,村本進司,山木幸子,許峰,馬蘭蘭,呉祖波,加藤伸郎
    • Organizer
      第42回神経科学学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Retrograde tracing study on dopaminergic innervations unto the CeA and BNST2019

    • Author(s)
      Zhao Qin, 山本亮,伊藤哲史,小野宗範,加藤伸郎
    • Organizer
      第42回神経科学学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Homerla-mediated resilience against neuronal hyperexcitability by APP and amyloid beta oligomer2018

    • Author(s)
      Kenji Yamamoto, Nobuo Kato
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Serotonergic modulation on the inhibitory synaptic transmission in the lateral amygdala.2018

    • Author(s)
      Ryo Yamamoto, Tokio Sugai, Nobuo Kato
    • Organizer
      48th Annual Meeting of Society for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of different parameter sets for photic stimulation designed to treat Alzheimer disease2018

    • Author(s)
      Nobuo Kato
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Simultaneous in vivo recording of the local field potential and the signal of fluorescent calcium indicator in the hippocampus of Altzheimer's mouse model.2018

    • Author(s)
      Ono M, Ohmori H, Xu F, Kato N.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Morphological analysis of the projection pattern from the hippocampus to the medial prefrontal cortex in Alzheimer mouse model.2018

    • Author(s)
      Feng Xu, Munenori Ono, Tetsufumi Ito, Nobuo Kato
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Serotonergic modulation on the inhibitory synaptic transmission in the lateral amygdala.2018

    • Author(s)
      Ryo Yamamoto, Tokio Sugai, Nobuo Kato
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 覚醒マウス下丘内の興奮性ニューロンと抑制性ニューロンの神経活動2018

    • Author(s)
      小野宗範、馬蘭蘭、加藤伸郎
    • Organizer
      日本音響学会聴覚研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Excitatory and inhibitory neural circuits in the auditory midbrain.2018

    • Author(s)
      Ono M
    • Organizer
      FAOPS 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 測光電極法を用いた海馬局所電位とカルシウム動態の同時記録2018

    • Author(s)
      小野宗範、大森治紀、許峰、呉祖波、加藤伸郎
    • Organizer
      第65回中部日本生理学会
    • Related Report
      2018 Annual Research Report
  • [Book] Neuron Types, Intrinsic Circuits, and Plasticity in the Inferior Colliculus.2018

    • Author(s)
      Ito T, Ono M, Oliver DL.
    • Total Pages
      26
    • Publisher
      Oxford University Press
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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