Neuronal mechanisms underlying synaptic and behavioral plasticity regulated by dopamine

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15936
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Nagase Masashi 東京慈恵会医科大学, 医学部, 助教 (40749462)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 扁桃体 / 腹側被蓋野 / 腕傍核 / シナプス可塑性 / ドーパミン

Outline of Final Research Achievements

While negative emotion, such as fear and pain, serves as an alarm signal of danger, dysregulation of the negative emotion is a critical clinical issue. However, neural circuitry mechanisms of regulation of negative emotion, in particular those mediated by neuromodulators, remain unknown. This study focused on dopamine and analyzed roles of a brainstem-midbrain-amygdala circuit to elucidate its physiological significance. We found modulation of mouse behavior by the activation of brainstem-midbrain pathway, induction of avoidance behavior by the activation of brainstem-amygdala pathway, modulatory effects of dopamine on the synaptic transmission in brainstem-amygdala pathway, and experience-dependent changes in taste preferences accompanied by plastic changes in the brainstem-midbrain-amygdala circuit.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

PTSDなどの精神疾患や慢性疼痛に伴う負情動の制御破綻は過度の苦痛をもたらし、QOLを著しく低下させて臨床上の大きな問題となるが、治療法が乏しいのが現状である。本研究では脳幹－腹側被蓋野－扁桃体神経回路による情動関連行動の制御や味覚情動価の変容に伴う可塑的変化、ドーパミンによる回路修飾を見出した。これらの結果は、負情動の制御破綻を伴う疾患に対して、脳幹－腹側被蓋野－扁桃体神経回路が治療標的となりうることを示すとともに、ドーパミン受容体を標的とする既存の薬物を用いた新たな治療戦略の開発に繋がることが期待される。