Endogenous opioid signaling in the retina modulates sleep/wake activity in mice.

Content Provider	Europe PMC
Author	Berezin, Casey-Tyler Bergum, Nikolas Luchini, Kes A. Curdts, Sierra Korkis, Christian Vigh, Jozsef
Copyright Year	2022
Description	Circadian sleep/wake rhythms are synchronized to environmental light/dark cycles in a process known as photoentrainment. We have previously shown that activation of β-endorphin-preferring μ-opioid receptors (MORs) inhibits the light-evoked firing of intrinsically photosensitive retinal ganglion cells (ipRGCs), the sole conduits of photoentrainment. Although we have shown that β-endorphin is expressed in the adult mouse retina, the conditions under which β-endorphin is expressed are unknown. Moreover, it is unclear whether endogenous activation of the MORs expressed by ipRGCs modulates the photoentrainment of sleep/wake cycles. To elucidate this, we first measured the mRNA expression of β-endorphin's precursor, proopiomelanocortin (POMC), at various times of day by quantitative reverse-transcription PCR. POMC mRNA appears to have cyclic expression in the mouse retina. We then studied β-endorphin expression with immunohistochemistry and found that retinal β-endorphin is more highly expressed in the dark/at night. Finally, we used telemetry to measure activity, EEG and EMG in freely moving animals to compare sleep/wake cycles in wild-type and transgenic mice in which only ipRGCs lack functional MORs. Results from these experiments suggest that the MORs expressed by ipRGCs contribute to the induction and maintenance of activity in the dark phase in nocturnal mice, via the promotion of wakefulness and inhibition of slow-wave sleep. Together, these data suggest that endogenous β-endorphin activates MORs expressed by ipRGCs to modulate sleep/wake activity via the photoentrainment pathway. Highlights • β-endorphin expression in the mouse retina is higher in the dark/at night. • Endogenous β-endorphin modulates sleep/wake through melanopsin ganglion cells. • μ-opioid receptors expressed by melanopsin ganglion cells influence sleep/wake.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9254600&blobtype=pdf
Volume Number	13
DOI	10.1016/j.nbscr.2022.100078
PubMed Central reference number	PMC9254600
PubMed reference number	35800978
Journal	Neurobiology of Sleep and Circadian Rhythms [Neurobiol Sleep Circadian Rhythms]
e-ISSN	24519944
Language	English
Publisher	Elsevier
Publisher Date	2022-06-26
Access Restriction	Open
Rights License	This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). © 2022 The Authors
Subject Keyword	Sleep/wake Telemetry μ-Opioid receptor β-endorphin Proopiomelanocortin Retina
Content Type	Text
Resource Type	Article
Subject	Neurology Pulmonary and Respiratory Medicine Behavioral Neuroscience Neurology (clinical)