Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells.
Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells.
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DOI：
10.1016/j.neuron.2014.12.030
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发表时间：
2015-01-21
期刊：
影响因子：
16.2
通讯作者：
Shah, Mala M.
中科院分区：
文献类型：
--
作者：
Martinello, Katiuscia;Huang, Zhuo;Lujan, Rafael;Tran, Baouyen;Watanabe, Masahiko;Cooper, Edward C.;Brown, David A.;Shah, Mala M.
乙酰胆碱严重影响依赖于大脑的学习。胆碱能纤维支配海马神经元轴突、树突和胞体。然而，乙酰胆碱对轴突信息处理的影响仍然未知。通过刺激胆碱能纤维和海马齿状回颗粒细胞的电生理记录，我们发现突触释放的乙酰胆碱优先降低动作电位阈值，增强内在兴奋性和突触电位-棘波耦合。这些影响持续至少30分钟后的刺激范例，是由于毒蕈碱受体激活。这导致轴突细胞内钙离子通过T型钙通道持续升高，如双光子成像所示。增强的Ca ~（2+）水平抑制轴突KV_7/M电流，降低尖峰阈值。在支持，免疫组织化学显示毒蕈碱M1受体，CaV3.2，和KV7.2/7.3亚基定位在颗粒细胞轴突。由于轴突信号的改变会影响神经元的放电模式和神经递质的释放，这是一种未报道的细胞机制，乙酰胆碱可能至少部分地增强认知过程。胆碱能纤维刺激引起尖峰阈值的持续降低突触后毒蕈碱受体激活增强轴突CaV3.2通道活性持续的Ca 2+内流抑制轴突KV 7通道，降低尖峰阈值较低的尖峰阈值增加动作电位产生的倾向乙酰胆碱被认为通过影响躯体-树突兴奋性和神经递质释放来影响认知过程。在这里，Martinello等人。表明内源性乙酰胆碱作用于轴突毒蕈碱受体，显著影响海马颗粒细胞动作电位的起始和信息处理。
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 KV7/M current, decreasing the spike threshold. In support, immunohistochemistry revealed muscarinic M1 receptor, CaV3.2, and KV7.2/7.3 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. Cholinergic fiber stimulation caused a persistent reduction in the spike threshold Post-synaptic muscarinic receptor activation enhanced axonal CaV3.2 channel activity The sustained Ca2+ entry inhibited axonal KV7 channels, lowering the spike threshold The lower spike threshold increased the propensity for action potential generation Acetylcholine is thought to influence cognitive processing by affecting somato-dendritic excitability and neurotransmitter release. Here, Martinello et al. show that endogenous acetylcholine acts on axonal muscarinic receptors to significantly influence action potential initiation and information processing in hippocampal granule cells.
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影响因子：
16.2
作者：
Bender, Kevin J.;Ford, Christopher P.;Trussell, Laurence O.
通讯作者：
Trussell, Laurence O.
影响因子：
25
作者：
Henze, DA;Wittner, L;Buzsáki, G
通讯作者：
Buzsáki, G
影响因子：
16.2
作者：
Gu Z;Yakel JL
通讯作者：
Yakel JL
影响因子：
5.3
作者：
Lee, MG;Hassani, OK;Jones, BE
通讯作者：
Jones, BE
DOI：
10.1038/npp.2010.104
发表时间：
2011-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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作者：
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