Carbachol excites sublaterodorsal nucleus neurons projecting to the spinal cord.
Carbachol excites sublaterodorsal nucleus neurons projecting to the spinal cord.
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卡巴胆碱兴奋投射到脊髓的侧背核神经元。
DOI：
10.1113/jphysiol.2013.261800
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Arrigoni,E
中科院分区：
文献类型：
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作者：
Weng,FJ;Williams,RH;Hawryluk,JM;Lu,J;Scammell,TE;Saper,CB;Arrigoni,E
关键点脊髓投射的下外侧背核（SLD）神经元的激活抑制运动活动，部分通过脊髓抑制性中间神经元，在快速眼动（REM）睡眠期间产生肌肉张力。长期以来，人们一直假设REM睡眠期间释放的乙酰胆碱通过激活SLD神经元导致REM睡眠张力。我们使用脑干切片的全细胞记录显示，乙酰胆碱通过M1和M3毒蕈碱受体直接兴奋脊髓投射SLD神经元，这些结果表明，乙酰胆碱通过兴奋脊髓投射的SLD神经元参与REM睡眠肌张力减退。长期以来，药理学证据表明乙酰胆碱在调节快速眼动（REM）睡眠中起着重要作用。例如，将胆碱能激动剂卡巴胆碱注射到脑桥背内侧会产生类似REM睡眠的状态，伴有肌肉张力不足和皮质激活，这两者都是REM睡眠的主要特征。位于脑桥的这个区域内的是背侧亚核（SLD），这是一种被认为是产生快速眼动睡眠肌肉弛缓所必需和充分的结构。多巴胺能SLD神经元的亚群通过向脊髓和延髓腹内侧运动相关甘氨酸能/GABA能神经元的下行投射，在REM睡眠期间有效地促进运动抑制。然而，先前的电生理和药理学研究检查乙酰胆碱对SLD神经元的影响，产生了相互矛盾的结果。在本研究中，我们试图阐明乙酰胆碱如何影响脊髓投射SLD（SLDsp）神经元的活动。我们使用逆行追踪结合膜片钳记录，并记录卡巴胆碱对SLDsp神经元的突触前和突触后作用。卡巴胆碱作用于突触前，通过增加突触能兴奋性微小突触后电流的频率。我们还发现卡巴胆碱通过激活Na+-Ca 2+交换器直接兴奋SLDsp神经元。突触前和突触后效应均由M1和M3毒蕈碱受体的共激活介导。这些观察结果表明，乙酰胆碱在SLDsp神经元上产生协同的、兴奋性的突触前和突触后反应，这反过来可能有助于促进REM睡眠期间的肌肉张力。
Key pointsActivation of spinally projecting sublaterodorsal nucleus (SLD) neurons inhibits motor activity, in part through spinal inhibitory interneurons, to produce muscle atonia during rapid‐eye‐movement (REM) sleep.It has long been hypothesized that acetylcholine released during REM sleep contributes to REM sleep atonia through activation of SLD neurons.We show, using whole‐cell recordings in brainstem slices, that acetylcholine directly excites spinally projecting SLD neurons via M1and M3muscarinic receptors, and increases afferent excitatory synaptic input to these neurons.These results suggest that acetylcholine contributes to REM sleep muscle atonia through excitation of spinally projecting SLD neurons.AbstractConsiderable electrophysiological and pharmacological evidence has long suggested an important role for acetylcholine in the regulation of rapid‐eye‐movement (REM) sleep. For example, injection of the cholinergic agonist carbachol into the dorsomedial pons produces an REM sleep‐like state with muscle atonia and cortical activation, both of which are cardinal features of REM sleep. Located within this region of the pons is the sublaterodorsal nucleus (SLD), a structure thought to be both necessary and sufficient for generating REM sleep muscle atonia. Subsets of glutamatergic SLD neurons potently contribute to motor inhibition during REM sleep through descending projections to motor‐related glycinergic/GABAergic neurons in the spinal cord and ventromedial medulla. Prior electrophysiological and pharmacological studies examining the effects of acetylcholine on SLD neurons have, however, produced conflicting results. In the present study, we sought to clarify how acetylcholine influences the activity of spinally projecting SLD (SLDsp) neurons. We used retrograde tracing in combination with patch‐clamp recordings and recorded pre‐ and postsynaptic effects of carbachol on SLDsp neurons. Carbachol acted presynaptically by increasing the frequency of glutamatergic miniature excitatory postsynaptic currents. We also found that carbachol directly excited SLDsp neurons by activating an Na+–Ca2+exchanger. Both pre‐ and postsynaptic effects were mediated by co‐activation of M1and M3muscarinic receptors. These observations suggest that acetylcholine produces synergistic, excitatory pre‐ and postsynaptic responses on SLDsp neurons that, in turn, probably serve to promote muscle atonia during REM sleep.