2013 Fiscal Year Final Research Report

Molecular mechanism of synapse differentiation and circuit formation by complex formation of secreted synapse organizer with its receptors

Research Project

Project/Area Number	23500469
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Neurophysiology and muscle physiology
Research Institution	Keio University
Principal Investigator	MATSUDA Keiko 慶應義塾大学, 医学部, 助教 (40383765)
Project Period (FY)	2011 – 2013
Keywords	シナプス形成 / シナプス可塑性 / 神経栄養因子
Research Abstract	We had proposed a new molecular mechanism underlying cerebellar parallel fiber synapse formation; secreted Cbln1 links its two receptors, GluD2 and Neurexin, across synaptic cleft, leading bidirectional synaptic differentiation. In hippocampal CA1 pyramidal neurons, most related receptor, GluD1 is restrictedly localized in TA layer which is the most distal part in CA1 dendrites, where GluD1 is responsible for establishment of LTD. Analysis in Cbln1 or Cbln4 knockout mice, restricted localization of GluD1 in TA layer requires its ligands Cbln1 and Cbln4. Thus we now propose the more general function of protein complex, Neurexin-Cbln-GluD in synapse formation and establishment of neuronal circuit precisely, not only in cerebellum but also in hippocampus.