Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area

Sasa Teng, Fenghua Zhen, Li Wang, Jose Canovas Schalchli, Jane Simko, Xinyue Chen, Hao Jin, Christopher D. Makinson and Yueqing Peng ()
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Sasa Teng: Columbia University
Fenghua Zhen: Columbia University
Li Wang: Columbia University
Jose Canovas Schalchli: Columbia University
Jane Simko: Columbia University
Xinyue Chen: Columbia University
Hao Jin: Columbia University
Christopher D. Makinson: Columbia University
Yueqing Peng: Columbia University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Understanding the neural mechanisms underlying sleep state transitions is a fundamental goal of neurobiology and important for the development of new treatments for insomnia and other sleep disorders. Yet, brain circuits controlling this process remain poorly understood. Here we identify a population of sleep-active glutamatergic neurons in the ventrolateral medulla (VLM) that project to the preoptic area (POA), a prominent sleep-promoting region, in mice. Microendoscopic calcium imaging demonstrate that these VLM glutamatergic neurons display increased activity during the transitions from wakefulness to Non-Rapid Eye Movement (NREM) sleep. Chemogenetic silencing of POA-projecting VLM neurons suppresses NREM sleep, whereas chemogenetic activation of these neurons promotes NREM sleep. Moreover, we show that optogenetic activation of VLM glutamatergic neurons or their projections in the POA initiates NREM sleep in awake mice. Together, our findings uncover an excitatory brainstem-hypothalamic circuit that controls the wake-sleep transitions.

Date: 2022
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DOI: 10.1038/s41467-022-32461-3

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