Choline-mediated depression of hippocampal synaptic transmission
Choline-mediated depression of hippocampal synaptic transmission
复制标题
胆碱介导的海马突触传递抑制
作者：
J. Mielke;T. Ahuja;T. Comas;G. Mealing
胆碱是维持细胞膜结构完整性所必需的微量营养素，它在突触处的存在要么是去极化诱导的突触前释放，要么是乙酰胆碱的降解。以往的研究使用全细胞记录表明，胆碱可以调节抑制性输入海马锥体神经元上发现的中间神经元上的烟碱乙酰胆碱受体（nAChRs）的作用。然而，很少有人知道胆碱如何影响神经元的活动，在人口水平，因此，我们使用细胞外记录，以评估其对突触传递急性准备海马切片的影响。胆碱以浓度依赖性方式（10、500和1000 µM）可逆性抑制诱发场兴奋性突触后电位（fEPSP）。当在诱导长时程增强后应用时，仍然观察到胆碱介导的抑制（CMD），并且增强在洗脱时返回。α7 nAChR拮抗剂不能完全阻断CMD，胆碱是其完全激动剂，但一般nAChR拮抗剂可能完全阻断CMD。胆碱增加成对脉冲促进的能力，以及应用γ-氨基丁酸（GABA）无法介导fEPSP的进一步抑制，表明胆碱作用的主要机制是促进神经递质释放。我们的研究提供的证据表明，胆碱可以抑制群体水平的活动，很可能是通过促进GABA从中间神经元的释放，从而影响海马功能。
Abstract 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-dependant 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.
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影响因子：
2.5
作者：
Ji, DY;Dani, JA
通讯作者：
Dani, JA
哺乳动物烟碱乙酰胆碱受体：从结构到功能。
影响因子：
33.6
作者：
Albuquerque EX;Pereira EF;Alkondon M;Rogers SW
通讯作者：
Rogers SW
影响因子：
24.8
作者：
Leuner B;Gould E
通讯作者：
Gould E
膳食胆碱补充增加了大鼠大脑中尼古丁结合位点的密度。
DOI：
--
发表时间：
1992
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Coutcher,JB;Cawley,G;Wecker,L
通讯作者：
Wecker,L
影响因子：
7.1
作者：
Zeisel, Steven H.
通讯作者：
Zeisel, Steven H.