Cholinergic Modulation of GABAergic and Glutamatergic Transmission in the Dorsal Subcoeruleus: Mechanisms for REM Sleep Control
Cholinergic Modulation of GABAergic and Glutamatergic Transmission in the Dorsal Subcoeruleus: Mechanisms for REM Sleep Control
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DOI：
10.1093/sleep/32.9.1135
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发表时间：
2009-09-01
期刊：
影响因子：
5.6
通讯作者：
Garcia-Rill, Edgar
中科院分区：
文献类型：
--
作者：
Heister, David S.;Hayar, Abdallah;Garcia-Rill, Edgar
研究目的：背侧蓝斑下（SubCD）神经元被认为促进PGO波，并在REM睡眠期间受到胆碱能传入的调制。我们研究了胆碱能激动剂卡巴胆碱（carbachol，CAR）对兴奋性和抑制性突触后电流（postsynaptic currents，PSCs）的不同作用，并研究了CAR在REM睡眠发育减少过程中对SubCD神经元的影响。设计：对7- 20日龄大鼠的脑干切片进行全细胞膜片钳记录。CAR通过烟碱和毒蕈碱M1受体诱导内向电流，直接作用于50%的SubCD神经元。CAR通过激活43%的SubCD细胞中的M2毒蕈碱受体诱导钾介导的外向电流。诱发刺激建立了NMDA，AMPA，GABA和甘氨酸能PSC在SubCD中的存在。发现CAR降低了34个SubCD细胞中31个的诱发EPSC振幅，但仅降低了测试的13个SubCD细胞中1个的诱发IPSC振幅。在记录的55%的细胞中，CAR降低了自发EPSC，而在27%的SubCD细胞中增加了自发IPSC。这些发现表明，CAR在SubCD中对快突触GABA能活性发挥主要的抑制作用，对快突触GABA能/甘氨酸能活性发挥主要的兴奋作用。我们假设在快速眼动睡眠期间，胆碱能“快动眼”投射到SubCD的神经元诱导抑制性中间神经元的兴奋和兴奋性事件的抑制，导致SubCD投射中产生协调活动神经元这些投射神经元的协调可能对产生快速眼动睡眠信号（如PGO波）至关重要。
Study Objectives: Dorsal subcoeruleus (SubCD) neurons are thought to promote PGO waves and to be modulated by cholinergic afferents during REM sleep. We examined the differential effect of the cholinergic agonist carbachol (CAR) on excitatory and inhibitory postsynaptic currents (PSCs), and investigated the effects of CAR on SubCD neurons during the developmental decrease in REM sleep.Design: Whole-cell patch clamp recordings were conducted on brain-stem slices of 7- to 20-day-old rats.Measurements and Results: CAR acted directly on 50% of SubCD neurons by inducing an inward current, via both nicotinic and muscarinic M1 receptors. CAR induced a potassium mediated outward current via activation of M2 muscarinic receptors in 43% of SubCD cells. Evoked stimulation established the presence of NMDA, AMPA, GABA, and glycinergic PSCs in the SubCD. CAR was found to decrease the amplitude of evoked EPSCs in 31 of 34 SubCD cells, but decreased the amplitude of evoked IPSCs in only 1 of 13 SubCD cells tested. Spontaneous EPSCs were decreased by CAR in 55% of cells recorded, while spontaneous IPSCs were increased in 27% of SubCD cells. These findings indicate that CAR exerts a predominantly inhibitory role on fast synaptic glutamatergic activity and a predominantly excitatory role on fast synaptic GABAergic/glycinergic activity in the SubCD.Conclusion: We hypothesize that during REM sleep, cholinergic "REM-on" neurons that project to the SubCD induce an excitation of inhibitory interneurons and inhibition of excitatory events leading to the production of coordinated activity in SubCD projection neurons. The coordination of these projection neurons may be essential for the production of REM sleep signs such as PGO waves.