A new early life stress model targeted to the lateral habenula: The mechanism of pshychiatric disorder evoked by experience

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17747
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience; Experimental pathology
• Research Institution: University of Toyama
• Principal Investigator: Nakamura Tomoya 富山大学, 大学院医学薬学研究部(医学), 助教 (70733343)
• Research Collaborator: 一條 裕之 富山大学, 医学部 解剖学講座, 教授
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: パルブアルブミン / 幼少期ストレス / 外側手綱核 / 不安 / うつ

Outline of Final Research Achievements

To know circuit mechanism by which anxiety and depression result from early-life stress, the pups were separated from dam for 3 hours/day during postnatal (P) 10-20 (Repeated maternal separation; RMS), and later on P60 their behaviors and stress-related regions: lateral habenula, hippocampus, and amygdala, are investigated. In the RMS group, it was observed that the smaller number of inhibitory parvalbumin positive cells and the higher neuronal activity under the stress specifically in the lateral habenula accompanying with the anxiety- and depression-like behaviors. Here we reveal that early-life stress causing behavioral alteration undermines the inhibitory circuits in lateral habenula.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

外界から影響を受け、経験が神経回路の構造と機能に効果を及ぼす幼少時期を臨界期と呼ぶが、情動の臨界期の存在はこれまで明らかではなく、情動の神経回路の発達と成熟の機構の知見は乏しかった。我々は、本研究において、情動の臨界期を実証的に検証できる動物モデルを確立し、幼少期ストレスに関連した不安様・うつ様症状の発症を見出した。本研究は情動の臨界期のさきがけとなる研究で、幼少期の経験の錯乱が情動の神経回路に与える影響を検証できた。