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The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light. We identified three peptidergic cell types that responded to light in the SCN: arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). In each cell type, light-responsive subgroups were enriched for expression of neuronal Per-Arnt-Sim (PAS) domain protein 4 (NPAS4) target genes. Further, mice lacking Npas4 had a longer circadian period under constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN. Our data indicate that NPAS4 is necessary for normal transcriptional responses to light in the SCN and critical for photic phase-shifting of circadian behavior.
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http://dx.doi.org/10.1016/j.neuron.2021.07.026 | DOI Listing |
Elife
September 2025
Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States.
Fragile X syndrome (FXS), a leading inherited cause of intellectual disability and autism, is frequently accompanied by sleep and circadian rhythm disturbances. In this study, we comprehensively characterized these disruptions and evaluated the therapeutic potential of a circadian-based intervention in the fragile X mental retardation 1 () knockout (KO) mouse. The KO mice exhibited fragmented sleep, impaired locomotor rhythmicity, and attenuated behavioral responses to light, linked to an abnormal retinal innervation and reduction of light-evoked neuronal activation in the suprachiasmatic nucleus.
View Article and Find Full Text PDFBiochem Biophys Rep
December 2025
Department of Animal Sciences, D.H. Barron Reproductive and Perinatal Biology Research Program, and Genetics Institute, University of Florida, Gainesville, FL, USA.
The circadian clock in the suprachiasmatic nucleus and peripheral tissues functions to regulate key physiological and cellular systems in a cycle approximating 24 h. Understanding the ontogeny of the circadian clock mechanism during mammalian development is incomplete. Accordingly, we used the mouse as a model and a previously published RNAseq dataset to determine when expression of core genes regulating the circadian clock increase in transcript abundance in fetal and postnatal brain, heart, liver, and kidney.
View Article and Find Full Text PDFCell Rep
September 2025
Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA; Division of Endocrinology & Metabolism, Department of Internal Medicine, UT Southwestern Medical C
Food consumption impacts body weight differently depending on the time of day. Here, we investigated whether suprachiasmatic nucleus (SCN) neurons responsive to the hormone ghrelin temporally regulate eating and body weight in mice. The chemogenetic stimulation of GHSR (growth hormone secretagogue receptor)-expressing SCN neurons during the mid-rest phase-when mice are most sensitive to ghrelin's orexigenic effects-increased food intake.
View Article and Find Full Text PDFiScience
September 2025
Department of Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA.
The current model for autonomous circadian oscillation is based on the transcriptional-translational feedback loops of circadian genes. The deletion of one of the circadian genes and its paralogs leads to arrhythmicity. triple knockout ( KO) mice exhibit arrhythmic behavior in constant darkness.
View Article and Find Full Text PDFNeurobiol Sleep Circadian Rhythms
November 2025
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
The suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, known as period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of the DNA methyltransferase inhibitor RG108 near the SCN.
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