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The retinal ipRGC-preoptic circuit mediates the acute effect of light on sleep
Open accessAbstract
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.
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While it has been hypothesized that ipRGCs engage VTA dopamine neurons via hypothalamic intermediates, the role of melanopsin in the dopaminergic response to light is unknown.
“While it has been hypothesized that ipRGCs engage VTA dopamine neurons via hypothalamic intermediates (Zhang et al., 2021), the role of melanopsin in the dopaminergic response to light is unknown.”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Zhang et al., 2021
The Results section, “Identification of the downstream targets of light-responsive POA neurons” (page unavailable), reports that light-responsive preoptic neurons form connections with the VTA, supporting a possible route from ipRGCs through a hypothalamic intermediary. It does not identify the VTA neurons receiving those connections as dopaminergic or show that ipRGCs engage them. The statement about melanopsin is not the part attributed to Zhang et al. by the citation. (LLM, conf=0.86)
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References 45 · Cited by 75
Research works printed but not linked: 1
- Paxinos, G. & Franklin, K. B. J. The mouse brain in stereotaxic coordinates, Compact 2nd edn. Elsevier Academic Press (2004).
Metadata
- Authors
- Zhang, Z., Beier, C., Weil, T., & Hattar, S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Zhang, Ze
- Venue
- Nature Communications
- Published
- 2021-08-25
- Volume
- 12
- Issue
- 1
- Pages
- 5115-5115
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8387462
- OpenAlex
- W3195115268
- Cited by
- 75
- References
- 45
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 19 · 2023: 16 · 2022: 15 · 2021: 1
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (ZIAMH002964-02)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- intrinsically photosensitive retinal ganglion cells, preoptic area, NREM sleep, REM sleep, corticotropin-releasing hormone neurons, suprachiasmatic nucleus, circadian rhythm, tuberomammillary nucleus, lateral hypothalamus, sleep regulation
- MeSH terms
- Animals, Light, Male, Neuronal Plasticity, Photoreceptor Cells, Preoptic Area, Retinal Ganglion Cells, Sleep, Suprachiasmatic Nucleus, Wakefulness, Mice
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