Sugar chain-based signals regulating morphological and functional synaptic plasticity in the cerebellum

2015 Fiscal Year Final Research Report

• Project Area: Deciphering sugar chain-based signals regulating integrative neuronal functions
• Project/Area Number: 23110009
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: Yuzaki Michisuke 慶應義塾大学, 医学部, 教授 (40365226)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA SHINJI 慶應義塾大学, 医学部, 講師 (60321816) ; MATSUDA KEIKO 慶應義塾大学, 医学部, 助教 (40383765)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: AMPA受容体 / エンドサイトーシス / エキソサイトーシス / LTD / LTP / 小脳 / ライソゾーム / マウス

Outline of Final Research Achievements

It is believed that long-term memory is initially stored as changes in the number of AMPA receptors at the postsynaptic sites and eventually converted into morphological changes at synapses for longer-term memory. However, molecular mechanisms underlying these processes have not been fully understood yet. Dendrites are surrounded by extracellular matrix (ECM) proteins, which are enriched with various sugar chains. Thus, AMPA receptor trafficking and morphological changes must be accompanied with changes of the surrounding ECM. In this study, we aimed to clarify how functional and morphological synaptic plasticity is regulated by the ECM in the cerebellum. We found that changes in neuronal activity induced AMPA receptor trafficking to/from lysosome-like organelle, which contained various kinds of glycosydase. Using a temporally-controlled gene knockout method, we also clarified how a single transcription factor regulated morphogenesis of spines and dendrites of Purkinje cells in vivo.

Free Research Field

神経生物学