The role of microglia in aberrant synaptic remodeling induced by peripheral nerve injury

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18995
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Ueta Yoshifumi 東京女子医科大学, 医学部, 助教 (00511015)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 体性感覚 / 脳幹 / 視床 / ミクログリア / シナプス

Outline of Final Research Achievements

Peripheral nerve injury rapidly reorganizes somatotopic maps in the adult brain. In mice, whisker deafferentation induces synaptic remodeling of ascending fibers on neurons in the barreloids of the ventral posteromedial (VPM) nucleus. VPM neurons receive multiple fibers derived not only from whisker but also from non-whisker regions of the brainstem, resulting in reorganized whisker map. However, it is unclear what mechanisms regulate this aberrant plasticity. Here I examine the involvement of microglia which are associated with formation and refinement of synapses. Microglial activity was increased in the whisker sensory pathway after the nerve injury. I found that the depletion of microglia suppressed nerve injury-induced synaptic remodeling in VPM.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

末梢神経の損傷は神経障害性疼痛や感覚機能の異常を引き起こし、これらに対する根本的治療法はいまだ確立されていない。これまでの多くの研究で、脳の感覚神経伝導路が可塑的な改編を受けることが、機能的な異常に重要な役割を果たすと考えられてきた。本研究は動物モデルを用いて詳細な回路機能を調べ、神経損傷に伴う体性感覚経路の改編を抑制する手段を見出した。この成果をさらに進展させることで、将来的には神経損傷に伴う機能異常を抑制する治療法の開発につながることが期待される。