Study on molecular mechanism of cerebellar circuit formation

2016 Fiscal Year Final Research Report

• Project/Area Number: 25290021
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Shinshu University
• Principal Investigator: UEMURA Takeshi 信州大学, 学術研究院医学系, 准教授 (00372368)
• Co-Investigator(Renkei-kenkyūsha): YOSHIDA Tomoyuki 富山大学, 医学薬学研究院, 准教授 (90372367)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 脳・神経 / 小脳 / 神経回路網構築

Outline of Final Research Achievements

Synapses are formed and maintained by trans-synaptic interaction between pre- and postsynaptic cell adhesion molecules. In the cerebellum, the trans-synaptic interaction of postsynaptic glutamate receptor GluRδ2 and presynaptic neurexins (Nrxns) through cerebellin precursor protein 1 (Cbln1) mediates parallel fiber (PF)-Purkinje cell (PC) synapse formation. In mammals, Nrxns are encoded by three genes (Nrxn1, Nrxn2, and Nrxn3). In this study, we generated cerebellar granule cell (GC)-specific Nrxn1, Nrxn2, and Nrxn3 triple KO mice. The cerebellar GCs-specific Nrxns triple KO mice showed severe ataxia and reduced cerebellar size. Histological analysis revealed that the number of cerebellar GCs was dramatically decreased in the cerebellar GCs-specific Nrxns triple KO mice. Electron microscopic analysis showed that PF-PC synapses were disappeared in the GCs-specific Nrxns triple KO mice. These results suggest that Nrxns are essential for cerebellar circuit formation.

Free Research Field

分子神経生物学、神経化学