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2021 Fiscal Year Final Research Report

The neural circuits and plasticity for adaptive behavior via neuropeptidergic modification

Research Project

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Project/Area Number 20K22694
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0704:Neuroscience, brain sciences, and related fields
Research InstitutionJikei University School of Medicine

Principal Investigator

Tohyama Suguru  東京慈恵会医科大学, 医学部, ポストドクトラルフェロー (20875520)

Project Period (FY) 2020-09-11 – 2022-03-31
Keywords恐怖記憶 / 情動 / シナプス可塑性 / 光遺伝学
Outline of Final Research Achievements

The central nucleus of the amygdala (CeA) plays a key role in processing sensory information from the internal and external environment, such as sounds and smells, contexts, and expressing adaptive emotional behaviors. However, the neural circuit mechanisms in the CeA that support adaptive behavior remain largely unknown. In this study, we aimed to elucidate the mechanisms of neural plasticity and the physiological functions in emotional regulation, focusing on the parabrachial-amygdaloid pathway (PB→CeA) via neuropeptidergic modification. Using in vivo optogenetics and behavioral pharmacology, we succeeded in artificial manipulation of the projection-specific plasticity in the CeA projecting PB neurons and found that neuropeptide-mediated modulation in PB→CeA in the maladaptation of the emotional behavior, such as dysregulation of emotional memory.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

様々な精神疾患や一見すると脳とはあまり関係のなさそうな代謝疾患や疼痛モデルにおいて扁桃体経路のシナプス増強や可塑性制御の破綻が観察されている。しかしながら、この経路における可塑性と行動変容との関係には未だ不明な点が多い。本研究では、光遺伝学を駆使して神経回路特異的な可塑性操作プロトコルを開発した。さらにこれに行動学的解析を組み合わせることで、可塑性の制御破綻と情動行動異常との因果関係を示唆する結果を得た。これらの成果は、ストレス関連疾患や代謝疾患において共通してみられる情動行動の異常病態をつなぐ脳内メカニズムや、将来的にはそれらの疾患に対する治療法開発のための基礎的知見となることが期待される。

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Published: 2023-01-30  

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