Elucidation of activity-dependency and molecular mechanisms of synapse elimination

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830004
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: The University of Tokyo
• Principal Investigator: UESAKA Naofumi 東京大学, 医学(系)研究科(研究院), 助教 (70597624)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: シナプス刈り込み / 小脳 / セマフォリン / Arc / 機能的神経回路形成 / スクリーニング

Outline of Final Research Achievements

In the present study, we have screened signaling molecules for synapse elimination in developing cerebellum during the period of elimination of redundant climbing fiber (CF) to Purkinje cell (PC) synapses, a representative case of synapse elimination in developing brain. We found that Arc mediates CF synapse elimination downstream of neural activity. In addition, two semaphorins, Sema3A and Sema7A, derived from postsynaptic PCs act as a synaptotoxin and a synaptotrophin, respectively, through their receptors on CFs. These findings have unraveled the long-unknown mechanism by which the information for eliminating or strengthening synapses is transmitted from postsynaptic cells to presynaptic cells. Our findings provide a new insight into the roles of semaphorins, a major family of intercellular signaling molecules known to play crucial roles in development of the nervous system, cell recognition in the immune system, and formation and regeneration of the bone.

Free Research Field

神経生理学