The neural mechanism of anxiety related long-term potentiation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19879
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: Hyogo Medical University
• Principal Investigator: KOGA KOHEI 兵庫医科大学, 医学部, 講師 (50768455)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: シナプス長期増強

Outline of Final Research Achievements

The anterior cingulate cortex (ACC) is a critical cortical area for various emotions, especially anxiety like behaviors. We focused on the presynaptic long-term potentiation (pre-LTP) that occurs to glutamatergic transmission in the ACC, and studied the detailed molecular mechanisms related to anxiety-like behaviors. Since an ubiquitin proteasome system (UPS) plays the role for the degradation of protein, we considered the UPS necessary for the cortical pre-LTP. Bath application of a proteasome inhibitor MG-132 inhibited the cortical pre-LTP. However, MG-132 did not affect basal synaptic transmission. An ubiquitin ligase E3, SCRRAPER knockout mice reduced pre-LTP. Furthermore, noradrenaline produced synaptic plasticity on glutamatergic transmission. These results suggest that the pre-LTP in the ACC which is related to anxiety like behaviors requires the UPS, especially through SCRAPPER.

Free Research Field

疼痛学

Academic Significance and Societal Importance of the Research Achievements

前帯状回は、情動の形成に重要な役割を果たす大脳皮質であり、不安に関与することがヒトイメージングで明らかになっている。我々が明らかにしたシナプスレベルの解析では、前帯状回のpre-LTPは興奮性神経伝達物質であるグルタミン酸の放出を促進することから、この神経伝達物質の放出が不安様行動の形成に関わる可能性が考えられる。本研究でpre-LTPやシナプス可塑性を制御する機構の詳細が明らかになると、不安障害や慢性疼痛による不安の増悪に対する創薬や治療法の開発につながっていく。