2021 Fiscal Year Final Research Report

Neural circuitry and decision making in the mouse olfactory system

Research Project

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Project/Area Number	17H06160
Research Category	Grant-in-Aid for Scientific Research (S)
Allocation Type	Single-year Grants
Research Field	Neurophysiology / General neuroscience
Research Institution	University of Fukui
Principal Investigator	Sakano Hitoshi 福井大学, 学術研究院医学系部門, 特命教授 (90262154)
Project Period (FY)	2017-05-31 – 2022-03-31
Keywords	嗅覚情報処理 / 情動・行動の出力判断 / 先天的な本能判断 / 刷り込み記憶と臨界期 / 神経回路の可塑的変化 / 神経疾患と発達障害
Outline of Final Research Achievements	In mice, early odor exposure affects social behaviors later in life. A signaling molecule, Semaphorin 7A, is induced in the odor-responding olfactory neurons in an activity-dependent manner. Plexin C1, a receptor for Sema7A, is expressed in second-order neurons, whose dendrite-localization is restricted to the first week after birth. Sema7A promotes post-synaptic events resulting in glomerular enlargement that causes an increase in sensitivity to the experienced odor. Neonatal odor experience also induces positive responses to the imprinted odor, even when the odor quality is innately aversive. Knockout and rescue experiments indicate that oxytocin in neonates is responsible for imposing positive quality on imprinted memory. If the oxytocin or Sema7A signaling is blocked in neonates, social interactions are impaired as adults. These results give new insights into our understanding of olfactory imprinting and will shed light on the neuro-developmental disorders.
Free Research Field	神経科学
Academic Significance and Societal Importance of the Research Achievements	本研究課題では、高等動物における情動・行動の出力判断をマウス嗅覚系を用いて神経回路レベルで解析し、ヒトの心の葛藤の問題に自然科学の立場で迫る試みを行なった。本研究では本能回路を中心に嗅覚神経配線の大筋を明らかにし、入力情報に対する価値付けのlogicsを解明した。本研究ではまた、この本能回路を介した先天的な行動出力が、臨界期の外界入力によって可塑的に変化する刷り込み現象の分子基盤を明らかにした。新生仔期の刷り込みは成長後の社会行動に大きな影響を持つ。感覚入力を臨界期に遮断すると、他個体を避ける行動異常が生じる。本研究で得られた成果は、発達障害の予防や改善に新たな道を拓くものと期待される。