Acetylcholine Boosts Dendritic NMDA Spikes in a CA3 Pyramidal Neuron Model.
Acetylcholine Boosts Dendritic NMDA Spikes in a CA3 Pyramidal Neuron Model.
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DOI：
10.1016/j.neuroscience.2021.11.014
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发表时间：
2022-05-01
期刊：
影响因子：
3.3
通讯作者：
O'Donnell C
中科院分区：
文献类型：
--
作者：
Humphries R;Mellor JR;O'Donnell C
已经提出乙酰胆碱通过增强CA 3-CA 3复发性突触的可塑性来促进海马CA 3网络内记忆集合的形成。CA 3神经元树突中的再生NMDA受体（NMDAR）激活（NMDA尖峰）增加突触Ca 2+内流，并可触发这种突触可塑性。乙酰胆碱抑制钾通道，从而增强树突的兴奋性，因此可以促进NMDA锋电位的产生。在这里，我们调查NMDAR介导的非线性突触整合在放射层（SR）和层腔隙分子（SLM）树突在重建的CA 3神经元计算模型，并研究这种非线性乙酰胆碱的影响。我们发现，远端SLM树突，具有更高的输入电阻，有一个较低的阈值NMDA尖峰生成相比SR树突。通过阻断钾通道（M型、A型、Ca 2+激活和内向整流）来模拟乙酰胆碱增加了树突的兴奋性，并减少了产生NMDA尖峰所需的突触数量，特别是在SR树突中。这种效应的大小在同一神经元内的不同树突分支之间是异质的。这些结果预测，乙酰胆碱促进树突整合和NMDA尖峰产生在选定的CA 3树突，可以加强特定的CA 3神经元之间的连接，形成记忆合奏。
Acetylcholine has been proposed to facilitate the formation of memory ensembles within the hippocampal CA3 network, by enhancing plasticity at CA3-CA3 recurrent synapses. Regenerative NMDA receptor (NMDAR) activation in CA3 neuron dendrites (NMDA spikes) increase synaptic Ca2+ influx and can trigger this synaptic plasticity. Acetylcholine inhibits potassium channels which enhances dendritic excitability and therefore could facilitate NMDA spike generation. Here, we investigate NMDAR-mediated nonlinear synaptic integration in stratum radiatum (SR) and stratum lacunosum moleculare (SLM) dendrites in a reconstructed CA3 neuron computational model and study the effect of acetylcholine on this nonlinearity. We found that distal SLM dendrites, with a higher input resistance, had a lower threshold for NMDA spike generation compared to SR dendrites. Simulating acetylcholine by blocking potassium channels (M-type, A-type, Ca2+-activated, and inwardly-rectifying) increased dendritic excitability and reduced the number of synapses required to generate NMDA spikes, particularly in the SR dendrites. The magnitude of this effect was heterogeneous across different dendritic branches within the same neuron. These results predict that acetylcholine facilitates dendritic integration and NMDA spike generation in selected CA3 dendrites which could strengthen connections between specific CA3 neurons to form memory ensembles.
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影响因子：
4.3
作者：
Bush D;Philippides A;Husbands P;O'Shea M
通讯作者：
O'Shea M
影响因子：
3.7
作者：
Degro CE;Kulik A;Booker SA;Vida I
通讯作者：
Vida I
影响因子：
16.2
作者：
Gu Z;Yakel JL
通讯作者：
Yakel JL
DOI：
10.1073/pnas.1317667111
发表时间：
2014-03-18
影响因子：
11.1
作者：
Brandalise, Federico;Gerber, Urs
通讯作者：
Gerber, Urs
影响因子：
16.6
作者：
Brandalise, Federico;Carta, Stefano;Helmchen, Fritjof;Lisman, John;Gerber, Urs
通讯作者：
Gerber, Urs