Cholinergic Afferent Stimulation Induces Axonal Function Plasticity in Adult Hippocampal Granule Cells

被引：80

作者：

Martinello, Katiuscia ^{[1
]}

Huang, Zhuo ^{[1
]}

Lujan, Rafael ^{[2
]}

Tran, Baouyen ^{[3
]}

Watanabe, Masahiko ^{[4
]}

Cooper, Edward C. ^{[3
]}

Brown, David A. ^{[5
]}

Shah, Mala M. ^{[1
]}

机构：

[1] UCL, UCL Sch Pharm, London WC1N 1AX, England

[2] Univ Castilla La Mancha, Dept Ciencias Med, Albacete 02006, Spain

[3] Baylor Coll Med, Houston, TX 77030 USA

[4] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido 0608638, Japan

[5] UCL, London WC1E 6BT, England

来源：

NEURON | 2015年 / 85卷 / 02期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

ACTION-POTENTIAL INITIATION; ANATOMICALLY IDENTIFIED NEURONS; IN-VIVO; MEMBRANE PHOSPHOINOSITIDES; ENHANCES EXCITABILITY; NETWORK OSCILLATIONS; PYRAMIDAL NEURONS; KV7; CHANNELS; ACETYLCHOLINE; THETA;

D O I：

10.1016/j.neuron.2014.12.030

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Acetylcholine critically influences hippocampal-dependent learning. Cholinergic fibers innervate hippocampal neuron axons, dendrites, and somata. The effects of acetylcholine on axonal information processing, though, remain unknown. By stimulating cholinergic fibers and making electrophysiological recordings from hippocampal dentate gyrus granule cells, we show that synaptically released acetylcholine preferentially lowered the action potential threshold, enhancing intrinsic excitability and synaptic potential-spike coupling. These effects persisted for at least 30 min after the stimulation paradigm and were due to muscarinic receptor activation. This caused sustained elevation of axonal intracellular Ca2+ via T-type Ca2+ channels, as indicated by two-photon imaging. The enhanced Ca2+ levels inhibited an axonal K(V)7/M current, decreasing the spike threshold. In support, immunohistochemistry revealed muscarinic M1 receptor, Ca(V)3.2, and K(V)7.2/7.3 subunit localization in granule cell axons. Since alterations in axonal signaling affect neuronal firing patterns and neurotransmitter release, this is an unreported cellular mechanism by which acetylcholine might, at least partly, enhance cognitive processing.

引用

页码：346 / 363

页数：18

共 47 条

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