The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.
The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.
复制标题
胆碱能激动剂卡巴胆碱可增加小鼠中缝背侧血清素能神经元自发 GABA 能突触电流的频率。
DOI：
10.1016/j.neuroscience.2013.11.005
复制
发表时间：
2014
期刊：
影响因子：
3.3
通讯作者：
Brown,RE
中科院分区：
文献类型：
--
作者：
Yang,C;Brown,RE
中隔背核（DRN） 5-羟色胺（5-HT）神经元在喂养、情绪控制和应激反应中起重要作用。在整个睡眠-觉醒周期中，它们活动的一个重要特征是，在快速眼动（REM）睡眠期间，它们的放电减少，这与脑干胆碱能神经元的觉醒/快速眼动-放电模式形成鲜明对比。一个著名的快速眼动睡眠控制模型假设了这些细胞群之间的相互作用。5-HT抑制胆碱能神经元，烟碱受体的激活可以激发DRN 5-HT神经元，但胆碱能对抑制输入的作用尚不完全清楚。在体外实验中，GAD67-GFP敲入小鼠DRN脑切片中，短暂（3分钟）的卡巴醇（50 μM）浸液增加了gfp阴性、推测的5-HT神经元中自发抑制突触后电流（sIPSCs）的频率，但不影响微型（河河鱼毒素不敏感）IPSCs。Carbachol没有直接的突触后效应。因此，碳乙醇可能会增加局部gaba能神经元的活性，这些神经元与5-HT神经元突触。去除包括腹外侧导水管周围灰质（vlPAG）区域在内的背侧区域，其中gaba能神经元投射到DRN，消除了碳脑醇对sIPSCs的影响，而去除包含脑桥网状核（PnO）的口区的腹侧区域则没有。此外，苯酚直接刺激gfp阳性、gaba能的vlPAG神经元。毒蕈碱受体和烟碱受体的拮抗作用完全消除了碳醇的作用。我们认为，当乙酰胆碱水平较低时，即在安静清醒和快速眼动睡眠开始时，胆碱能神经元抑制DRN 5-HT神经元，部分原因是位于局部vlPAG和DRN gaba能神经元上的毒碱和烟碱受体的兴奋。高放电率或突发放电的胆碱能神经元与注意清醒或阶段性快速眼动睡眠期间导致5-HT神经元的兴奋通过激活烟碱受体位于突触后和突触前兴奋传入。
Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep–wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here,in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via the activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents.