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

• 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
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• 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 / 神経可塑性 / 母子分離ストレス / 神経活動性 / 抑制性神経細胞 / 不安様行動 / ペリニューロナルネット

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.

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。

Research Products

• [Presentation] Structure and function of the LHb are regioselectively altered under the influences of early-life stress (2018)
  • Author(s): 中村友也
  • Organizer: 第４１回日本神経科学大会
  • Int'l Joint Research
• [Presentation] 幼少期外側手綱核のストレスに対する臨界期様現象；神経機構解析 (2018)
  • Author(s): 中村友也
  • Organizer: Toyama Science GALA 2018
• [Presentation] Lateral habenular structure and function of adult under the influence of early-life stress (2017)
  • Author(s): 黒嵜公平、中村友也、兼本宗則、一條裕之
  • Organizer: 第40回日本神経科学大会
  • Int'l Joint Research