School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, Canada.
Nutr Neurosci. 2011 Sep;14(5):186-94. doi: 10.1179/1476830511Y.0000000010.
Choline is a micronutrient essential for the structural integrity of cellular membranes, and its presence at synapses follows either depolarization-induced pre-synaptic release or degradation of acetylcholine. Previous studies using whole-cell recording have shown that choline can modulate inhibitory input to hippocampal pyramidal neurons by acting upon nicotinic acetylcholine receptors (nAChRs) found on interneurons. However, little is known about how choline affects neuronal activity at the population level; therefore, we used extracellular recordings to assess its influence upon synaptic transmission in acutely prepared hippocampal slices. Choline caused a reversible depression of evoked field excitatory post-synaptic potentials (fEPSPs) in a concentration-dependent manner (10, 500, and 1000 µM). When applied after the induction of long-term potentiation, choline-mediated depression (CMD) was still observed, and potentiation returned on wash-out. Complete blockade of CMD could not be achieved with antagonists for the α7 nAChR, to which choline is a full agonist, but was possible with a general nAChR antagonist. The ability of choline to increase paired-pulse facilitation, and the inability of applied gamma-aminobutyric acid (GABA) to mediate further depression of fEPSPs, suggests that the principal mechanism of choline's action was on the facilitation of neurotransmitter release. Our study provides evidence that choline can depress population-level activity, quite likely by facilitating the release of GABA from interneurons, and may thereby influence hippocampal function.
胆碱是一种必需的微量营养素，对于细胞膜的结构完整性至关重要，其在突触中的存在遵循去极化诱导的前突触释放或乙酰胆碱的降解。以前使用全细胞记录的研究表明，胆碱可以通过作用于神经元上的烟碱型乙酰胆碱受体（nAChRs）来调节海马锥体神经元的抑制性输入。然而，对于胆碱如何影响群体水平的神经元活动知之甚少；因此，我们使用细胞外记录来评估其对急性制备的海马切片中突触传递的影响。胆碱以浓度依赖的方式（10、500 和 1000 µM）可逆地抑制诱发的场兴奋性突触后电位（fEPSP）。当在长时程增强诱导后应用时，仍观察到胆碱介导的抑制（CMD），并且在洗涤后增强恢复。用胆碱的完全激动剂α7 nAChR 的拮抗剂不能完全阻断 CMD，但用一般的 nAChR 拮抗剂可以阻断。胆碱增加成对脉冲易化的能力，以及应用 GABA 不能进一步抑制 fEPSP 的能力表明，胆碱作用的主要机制是促进神经递质释放。我们的研究提供了证据表明，胆碱可以抑制群体水平的活动，很可能是通过促进神经元 GABA 的释放，从而可能影响海马功能。
