Calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP

作     者：Lu, YM Mansuy, IM Kandel, ER Roder, J 

作者机构：Columbia Univ Coll Phys & Surg Ctr Neurobiol & Behav Howard Hughes Med Inst New York NY 10032 USA Univ Toronto Mt Sinai Hosp Samuel Lunenfeld Res Inst Dept Mol & Med Genet Toronto ON M5S 1A8 Canada 

出 版 物：《NEURON》 (神经元)

年 卷 期：2000年第26卷第1期

页      面：197-205页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学] 

基　　金：National Institutes of Mental Health Howard Hughes Medical Institute, HHMI Ontario Neurotrauma Foundation, ONF University of Toronto, UofT Medical Research Council Canada, MRC 

主　　题：荷包牡丹碱/药理学 钙神经素/药物作用 钙神经素/生理学 酶抑制剂/药理学 兴奋性突触后电位/药物作用 兴奋性突触后电位/生理学 GABA拮抗剂/药理学 免疫抑制剂/药理学 长时程增强/药物作用 长时程增强/生理学 小鼠 转基因 黑软海绵素A/药理学 锥体细胞/药物作用 锥体细胞/生理学 大鼠 Sprague-Dawley 受体 GABA-A/药物作用 受体 GABA-A/生理学 受体 N-甲基-D-天冬氨酸/药物作用 受体 N-甲基-D-天冬氨酸/生理学 他罗利姆/药理学 动物 小鼠 大鼠 

摘      要：Coincident pre- and postsynaptic activity generates long-term potentiation (LTP), a possible cellular model of learning and memory. LTP has two components: (1) an increase in the excitatory postsynaptic potential (EPSP), and (2) an increase in the ability of the EPSP to generate a spike (ES coupling of LTP). We have used pharmacological and genetic approaches to address the molecular nature of E-S coupling in CA1 pyramidal neurons. Blockade of the Ca2+-sensitive phosphatase, calcineurin, prevents induction of ES coupling without interfering with LTP of the EPSP. Calcineurin produces its effect on E-S coupling by inducing a long-lasting depression (LTD) of the GABA,mediated inhibitory postsynaptic potentials (IPSPs). This LTD of the IPSP was prevented by blockade of NMDA receptors. Thus, the tetanus that elicits NMDA-dependent LTP mediates a coordinately regulated double function. It produces LTP of the EPSP and, concomitantly, LTD of the IPSP that leads to enhancement of E-S coupling.