A Discrete Glycinergic Neuronal Population in the Ventromedial Medulla That Induces Muscle Atonia during REM Sleep and Cataplexy in Mice
A Discrete Glycinergic Neuronal Population in the Ventromedial Medulla That Induces Muscle Atonia during REM Sleep and Cataplexy in Mice
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DOI：
10.1523/jneurosci.0688-20.2020
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发表时间：
2021-02-17
影响因子：
5.3
通讯作者：
Sakurai, Takeshi
中科院分区：
文献类型：
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作者：
Uchida, Shuntaro;Soya, Shingo;Sakurai, Takeshi
在快速眼动（REM）睡眠期间，由于躯体运动神经元受到下行抑制通路的抑制，反重力肌张力和身体运动大多不存在。最近的研究表明，延髓腹内侧区的甘氨酸/GABA神经元（VMM; Gly（VMM）神经元）在REM睡眠（REM-atonia）期间产生肌张力（REM-atonia）中起重要作用。然而，这些REM-张力缺乏诱导神经元如何与其他神经元群体互连一直是未知的。在本研究中，我们首先确定了一个特定的亚群的甘氨酸（VMM）神经元，在诱导REM-弛缓症的病毒载体介导的跟踪在雄性小鼠中，甘氨酸能神经元表达Cre重组酶发挥重要作用。我们发现这些神经元接受来自几个脑干区域的神经元的直接突触输入，包括背侧被盖下核（SLD; Glu（SLD）神经元）中的谷氨酸能神经元。通过特异性表达破伤风毒素轻链（TeTNLC）来沉默这一回路，导致REM睡眠没有张力不足。当应用于发作性睡眠食欲素-共济失调蛋白-3小鼠时，这种操作还引起在昏厥样发作（克莱斯）中花费的时间显著减少。我们还发现Gly（VMM）神经元在维持睡眠中起着重要作用。本研究在VMM中鉴定了一群甘氨酸能神经元，它们通常参与REM-弛缓和紧张症。
During rapid eye movement (REM) sleep, anti-gravity muscle tone and bodily movements are mostly absent, because somatic motoneurons are inhibited by descending inhibitory pathways. Recent studies showed that glycine/GABA neurons in the ventromedial medulla (VMM; Gly(VMM) neurons) play an important role in generating muscle atonia during REM sleep (REM-atonia). However, how these REM-atonia-inducing neurons interconnect with other neuronal populations has been unknown. In the present study, we first identified a specific subpopulation of Gly(VMM) neurons that play an important role in induction of REM-atonia by virus vector-mediated tracing in male mice in which glycinergic neurons expressed Cre recombinase. We found these neurons receive direct synaptic input from neurons in several brain stem regions, including glutamatergic neurons in the sublaterodorsal tegmental nucleus (SLD; Glu(SLD) neurons). Silencing this circuit by specifically expressing tetanus toxin light chain (TeTNLC) resulted in REM sleep without atonia. This manipulation also caused a marked decrease in time spent in cataplexy-like episodes (CLEs) when applied to narcoleptic orexin-ataxin-3 mice. We also showed that Gly(VMM) neurons play an important role in maintenance of sleep. This present study identified a population of glycinergic neurons in the VMM that are commonly involved in REM-atonia and cataplexy.