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.

SIGNIFICANCE STATEMENT We identified a population of glycinergic neurons in the ventral medulla that plays an important role in inducing muscle atonia during rapid eye movement (REM) sleep. It sends axonal projections almost exclusively to motoneurons in the spinal cord and brain stem except to those that innervate extraocular muscles, while other glycinergic neurons in the same region also send projections to other regions including monoaminergic nuclei. Furthermore, these neurons receive direct inputs from several brainstem regions including glutamatergic neurons in the sublaterodorsal tegmental nucleus (SLD). Genetic silencing of this pathway resulted in REM sleep without atonia and a decrease of cataplexy when applied to narcoleptic mice. This work identified a neural population involved in generating muscle atonia during REM sleep and cataplexy.

在快速眼动 (REM) 睡眠期间，反重力肌肉张力和身体运动大多不存在，因为躯体运动神经元受到下行抑制通路的抑制。最近的研究表明，腹内侧髓质中的甘氨酸/GABA 神经元（VMM；Gly ^VMM神经元）在 REM 睡眠（REM-atonia）期间在产生肌肉张力障碍方面发挥着重要作用。然而，这些诱导快速眼动肌张力障碍的神经元如何与其他神经元群相互连接尚不清楚。在本研究中，我们首先确定了 Gly ^VMM的特定亚群在甘氨酸能神经元表达 Cre 重组酶的雄性小鼠中，病毒载体介导的示踪在诱导 REM 张力障碍中起重要作用的神经元。我们发现这些神经元从几个脑干区域的神经元接收直接的突触输入，包括背外侧被盖核中的谷氨酸能神经元（SLD；Glu ^SLD神经元）。通过特异性表达破伤风毒素轻链 (TeTNLC) 使该回路静音，导致 REM 睡眠没有张力障碍。当应用于发作性睡病orexin-ataxin-3小鼠时，这种操作还导致猝倒样发作 (CLE) 花费的时间显着减少。我们还表明 Gly ^VMM神经元在维持睡眠中起重要作用。本研究确定了 VMM 中的一组甘氨酸能神经元，这些神经元通常与 REM 张力障碍和猝倒有关。

意义声明我们在腹侧髓质中发现了一群甘氨酸能神经元，它们在快速眼动 (REM) 睡眠期间在诱导肌肉张力失衡中起重要作用。它几乎只向脊髓和脑干中的运动神经元发送轴突投射，除了那些支配眼外肌的运动神经元，而同一区域的其他甘氨酸能神经元也将投射发送到其他区域，包括单胺能核。此外，这些神经元接收来自几个脑干区域的直接输入，包括背外侧被盖核 (SLD) 中的谷氨酸能神经元。当应用于发作性睡病小鼠时，该途径的遗传沉默导致无张力障碍的 REM 睡眠和猝倒减少。这项工作确定了一个参与在 REM 睡眠和猝倒期间产生肌肉张力障碍的神经群体。