Action potential regulation at the node of Ranvier and perineuronal nets' regulation of GABAergic transmission in the deep cerebellar nuclei

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Doshisha University
• Principal Investigator: Hirono Moritoshi 同志社大学, 研究開発推進機構, 准教授 (30318836)
• Co-Investigator(Renkei-kenkyūsha): MISONOU Hiroaki 同志社大学, 脳科学研究科, 教授 (40609509) ; WATANABE Shoji 同志社大学, 研究開発推進機構, 助教 (80462745) ; YANAGAWA Yuchio 群馬大学, 大学院医学系研究科, 教授 (90202366) ; HIRAI Hirokazu 群馬大学, 大学院医学系研究科, 教授 (70291086)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 活動電位 / パラノード / BKチャネル / プルキンエ細胞 / 小脳核 / 細胞外マトリックス / ペリニューロナルネット / 瞬目反射条件づけ

Outline of Final Research Achievements

Regulation of axonal action potentials (APs) by K+ channels is important in the CNS. Application of BK channel blockers and T-type Ca2+ channel blockers to axons of cerebellar Purkinje cells (PCs) increased the failure rate of antidromic APs, suggesting that paranodal BK channels support high-fidelity firing at the node of Ranvier. Perineuronal nets (PNNs) are the extracellular matrix of neurons and are found around large neurons in the deep cerebellar nuclei (DCN). Enzymatic PNN depletion of DCN neurons reduced the paired-pulse ratio of inhibitory postsynaptic currents (IPSCs) and increased the miniature IPSC frequency without changing the amplitude, suggesting that PNN depletion enhances GABA release from presynaptic terminals. Mice having received the enzyme in the interpositus nuclei exhibited a higher conditioned response rate in delay eyeblink conditioning than control mice, suggesting that PNNs suppress GABAergic transmission and impede motor learning in the adult cerebellum.

Free Research Field

神経薬理