Neural circuit mechanism underlying autonomic nervous responses to unpleasant emotions

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19477
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 51:Brain sciences and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Matsumoto Masayuki 筑波大学, 医学医療系, 研究員 (50577864)
• Co-Investigator(Kenkyū-buntansha): 小金澤 禎史 筑波大学, 医学医療系, 准教授 (80431691)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 外側手綱核 / ドーパミン / セロトニン / 自律神経系

Outline of Final Research Achievements

This study attempted to understand the neural circuit mechanism underlying autonomic nervous responses to unpleasant emotions. We first found that electrical stimulation of the lateral habenula, which is involved in the induction of unpleasant emotions, modulates blood circulation control and respiratory motor control, which are innervated by autonomic nerves. We also found that systemic administration of dopamine receptor antagonists and serotonin receptor antagonists reduces the modulation effect caused by the electrical stimulation. Furthermore, inactivation of the ventral tegmental area, one of the origins of the dopamine nervous system, also reduced this effect. These findings suggest that the neural circuits that project from the lateral habenula to the dopamine nervous system (particularly in the ventral tegmental area) and the serotonergic nervous system play crucial roles in autonomic nervous control.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

外側手綱核と鬱病やPTSDとの関係が注目されてきた。たとえば外側手綱核をターゲットにした脳深部刺激療法が重度の鬱の治療に効果があることが報告されるなど、臨床応用に向けた取り組みが進んでいる。その一方、鬱病やPTSDで異常が見られる自律神経機能に対する外側手綱核の役割は不明なままである。身体の恒常性維持にとって重要な自律神経機能の異常は、動悸や不眠、拒食/過食、通勤通学の困難など様々な身体性、情動性の症状につながる。外側手綱核からドーパミン神経系やセロトニン神経系への投射が自律神経制御に重要であることを示した本研究の成果は、これらの症状に対して有効な治療法の開発につながることが期待できる。