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<p>Sleep suppresses most motor output, yet rapid eye movement sleep (REMs) is marked by brief muscle twitches, including eye movements (EMs), indicating selective motor preservation. How these opposing features are coordinated remains unclear. Here we show that cholinergic neurons in the oculomotor nucleus (nIII<sup>ChAT</sup>) possess dual functional organization governing REMs termination and oculomotor execution in mice. We identify a ventrolateral periaqueductal gray-projecting nIII<sup>ChAT</sup> subset whose activity dissociates from EMs but undergoes a progressive increase prior to REMs termination. Optogenetic activation of this subset suppresses REMs without affecting EMs, whereas extraocular muscles-projecting nIII<sup>ChAT</sup> neurons reliably induced EMs without altering sleep-wake states. These motor and sleep-modulating functions of nIII<sup>ChAT</sup> neurons are coordinated by genetically distinct <i>Vglut2</i>- and <i>Vgat</i>-expressing neurons in the upstream nucleus papilio. Collectively, our findings revealed a microcircuitry underlying REMs exit, where motor related function of nIII is preparing the mammal to enter the subsequent wakefulness with elevated motor capabilities.</p>

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Parallel cholinergic circuit in oculomotor nucleus to control eye movements and REM sleep

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Chengyong Jiang,
  • Yuanyuan Luo,
  • Xinrong Tan,
  • Hongtao Wang,
  • Qingshuo Meng,
  • Yanyu Xiong,
  • Er Chen,
  • Yuqing Chen,
  • Liyuan Cui,
  • Zhili Huang,
  • Biao Yan,
  • Jiayi Zhang

摘要

Sleep suppresses most motor output, yet rapid eye movement sleep (REMs) is marked by brief muscle twitches, including eye movements (EMs), indicating selective motor preservation. How these opposing features are coordinated remains unclear. Here we show that cholinergic neurons in the oculomotor nucleus (nIIIChAT) possess dual functional organization governing REMs termination and oculomotor execution in mice. We identify a ventrolateral periaqueductal gray-projecting nIIIChAT subset whose activity dissociates from EMs but undergoes a progressive increase prior to REMs termination. Optogenetic activation of this subset suppresses REMs without affecting EMs, whereas extraocular muscles-projecting nIIIChAT neurons reliably induced EMs without altering sleep-wake states. These motor and sleep-modulating functions of nIIIChAT neurons are coordinated by genetically distinct Vglut2- and Vgat-expressing neurons in the upstream nucleus papilio. Collectively, our findings revealed a microcircuitry underlying REMs exit, where motor related function of nIII is preparing the mammal to enter the subsequent wakefulness with elevated motor capabilities.