Choline induces opposite changes in pyramidal neuron excitability and synaptic transmission through a nicotinic receptor-independent process in hippocampal slices
Choline induces opposite changes in pyramidal neuron excitability and synaptic transmission through a nicotinic receptor-independent process in hippocampal slices
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DOI：
10.1007/s00424-017-1939-5
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发表时间：
2017-06-01
影响因子：
4.5
通讯作者：
Hernandez-Guijo, J. M.
中科院分区：
文献类型：
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作者：
Albinana, E.;Luengo, J. G.;Hernandez-Guijo, J. M.
胆碱作为乙酰胆碱降解的产物存在于胆碱能突触中。此外，它被认为是α 5和α 7烟碱乙酰胆碱受体（nAChR）的选择性激动剂。在这项研究中，我们确定了胆碱如何影响动作电位和兴奋性突触传递使用细胞外和细胞内记录技术在CA1区的海马脑片从小鼠和大鼠。胆碱以浓度依赖性方式引起诱发场兴奋性突触后电位（fEPSP）的可逆性抑制，而α 7 nAChR拮抗剂不影响该抑制。此外，这种胆碱诱导的作用不能被α 7 nAChR的选择性激动剂或变构调节剂模拟。此外，这种胆碱介导的作用不能被GABA受体的选择性拮抗剂或胆碱摄取抑制剂hemicholinium阻止。配对脉冲易化范式，检测是否一种物质影响突触前释放谷氨酸，没有修改胆碱。另一方面，胆碱诱导了一个强大的增加人口穗诱发的顺向刺激，但没有修改诱发的逆向刺激。我们还发现，胆碱受损的复发性抑制记录在锥体细胞层通过一种机制独立的α 7 nAChR激活。这些胆碱介导的影响fEPSP和人口穗观察到大鼠脑片中完全复制从α 7 nAChR基因敲除小鼠，这加强了我们的结论，胆碱调节突触传递和神经元兴奋性的机制独立于烟碱受体激活。
Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selective agonist for alpha 5 and alpha 7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using extracellular and intracellular recording techniques in CA1 area of hippocampal slices obtained from both mice and rats. Choline caused a reversible depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner that was not affected by alpha 7 nAChR antagonists. Moreover, this choline-induced effect was not mimicked by either selective agonists or allosteric modulators of alpha 7 nAChRs. Additionally, this choline-mediated effect was not prevented by either selective antagonists of GABA receptors or hemicholinium, a choline uptake inhibitor. The paired pulse facilitation paradigm, which detects whether a substance affects presynaptic release of glutamate, was not modified by choline. On the other hand, choline induced a robust increase of population spike evoked by orthodromic stimulation but did not modify that evoked by antidromic stimulation. We also found that choline impaired recurrent inhibition recorded in the pyramidal cell layer through a mechanism independent of alpha 7 nAChR activation. These choline-mediated effects on fEPSP and population spike observed in rat slices were completely reproduced in slices obtained from alpha 7 nAChR knockout mice, which reinforces our conclusion that choline modulates synaptic transmission and neuronal excitability by a mechanism independent of nicotinic receptor activation.