Involvement of glutamate transporters in central stress response

2017 Fiscal Year Final Research Report

• Project/Area Number: 26430003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Gunma University
• Principal Investigator: Hiroki Yasuda 群馬大学, 大学院医学系研究科, 准教授 (60294071)
• Co-Investigator(Renkei-kenkyūsha): MUKAI Hideyuki 神戸大学, 医学系研究科, 准教授 (80252758) ; OHNISHI Hiroshi 群馬大学, 大学院保健学研究科, 教授 (70334125)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: repeated swim / 海馬歯状回 / 顆粒細胞 / 神経型グルタミン酸トランスポーター / protein kinase N / 代謝型グルタミン酸受容体 / ストレス

Outline of Final Research Achievements

Functions of group 1 metabotropic glutamate receptors (mGluRs) should be restricted within normal range, otherwise brain disorders could develop. Here we report that neuronal protein kinase N1 (PKN1) normalizes excitability of dentate granule cells in the hippocampus through decreasing group 1 mGluR activity by upregulating neuronal glutamate transporters, and controls anxiety. Knocking out PKN1 in the mature dentate gyrus of the hippocampus induced group 1 mGluR-dependent hyperexcitability that was also observed in stressed dentate granule cells in the wild-type hippocampus. Inhibiting glutamate transporter by DL-TBOA elevated neuronal excitability in wild-type mice, but not in KO mice, suggesting that all the electrophysiological phenotypes in PKN1 KO mice were mimicked and occluded by inhibition of glutamate transporters. Thus, PKN1 is critical for regulating neuronal excitability through normalization of mGluR functions. We also present behavioral features in PKN1a KO mice.

Free Research Field

神経生理学