The retinal ipRGC-preoptic circuit mediates the acute effect of light on sleep

Ze Zhang,Tenley Weil,Corinne Beier,Samer Hattar

doi:10.1038/s41467-021-25378-w

Ze Zhang, Tenley Weil + Show 2 more

Open Access

https://doi.org/10.1038/s41467-021-25378-w

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Abstract

Light regulates daily sleep rhythms by a neural circuit that connects intrinsically photosensitive retinal ganglion cells (ipRGCs) to the circadian pacemaker, the suprachiasmatic nucleus. Light, however, also acutely affects sleep in a circadian-independent manner. The neural circuits involving the acute effect of light on sleep remain unknown. Here we uncovered a neural circuit that drives this acute light response, independent of the suprachiasmatic nucleus, but still through ipRGCs. We show that ipRGCs substantially innervate the preoptic area (POA) to mediate the acute light effect on sleep in mice. Consistently, activation of either the POA projecting ipRGCs or the light-responsive POA neurons increased non-rapid eye movement (NREM) sleep without influencing REM sleep. In addition, inhibition of the light-responsive POA neurons blocked the acute light effects on NREM sleep. The predominant light-responsive POA neurons that receive ipRGC input belong to the corticotropin-releasing hormone subpopulation. Remarkably, the light-responsive POA neurons are inhibitory and project to well-known wakefulness-promoting brain regions, such as the tuberomammillary nucleus and the lateral hypothalamus. Therefore, activation of the ipRGC-POA circuit inhibits arousal brain regions to drive light-induced NREM sleep. Our findings reveal a functional retina-brain circuit that is both necessary and sufficient for the acute effect of light on sleep.

Highlights

Light regulates daily sleep rhythms by a neural circuit that connects intrinsically photosensitive retinal ganglion cells to the circadian pacemaker, the suprachiasmatic nucleus
We found that light-responsive neurons in the preoptic area (POA) form monosynaptic connections with some of the known downstream targets of the POA, including the tuberomammillary nucleus (TMN), the lateral hypothalamus (LH) (Fig. 5d, g), the ventral tegmental area (VTA) (Fig. 5e, h), and the dorsal raphe nucleus (DRN) (Fig. 5f, i), which are regions well-known for wakefulness promotion
Our findings suggest that this circuit acts through the inhibition of the TMN, the LH, the VTA and the DRN, areas known for wakefulness-promoting functions[15,25,35,36,37,38,39,40,41,42,43]

Summary

Introduction

Light regulates daily sleep rhythms by a neural circuit that connects intrinsically photosensitive retinal ganglion cells (ipRGCs) to the circadian pacemaker, the suprachiasmatic nucleus. We uncovered a neural circuit that drives this acute light response, independent of the suprachiasmatic nucleus, but still through ipRGCs. We show that ipRGCs substantially innervate the preoptic area (POA) to mediate the acute light effect on sleep in mice. Activation of the ipRGC-POA circuit inhibits arousal brain regions to drive light-induced NREM sleep. Activation of the ipRGCs that project to the POA or activation of the light-responsive POA neurons themselves both increase the amount of non-rapid eye movement (NREM) sleep. Our study reveals that a neural circuit from ipRGCs to the POA is predominantly responsible for the acute effect of light on NREM sleep

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