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Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we identify a novel, direct connection between the DA neurons of the ventral tegmental area (VTA) and the suprachiasmatic nucleus (SCN). We demonstrate that D1 dopamine receptor (Drd1) signaling within the SCN is necessary for properly timed resynchronization of activity rhythms to phase-shifted light:dark cycles and that elevation of DA tone through selective activation of VTA DA neurons accelerates photoentrainment. Our findings demonstrate a previously unappreciated role for direct DA input to the master circadian clock and highlight the importance of an evolutionarily significant relationship between the circadian system and the neuromodulatory circuits that govern motivational behaviors.
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http://dx.doi.org/10.1016/j.cub.2017.06.084 | DOI Listing |
Cell 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.
View Article and Find Full Text PDFJ Biol Rhythms
August 2025
Surrey Sleep Research Centre, Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK.
Biomarkers are valuable tools in a wide range of human health areas including circadian medicine. Valid, low-burden, multivariate molecular approaches to assess circadian phase at scale in people living and working in the real world hold promise for translating basic circadian knowledge to practical applications. However, standards for the development and evaluation of these circadian biomarkers have not yet been established, even though several publications report such biomarkers and claim that the methods are universal.
View Article and Find Full Text PDFBiomedicines
August 2025
Neurochemistry Department, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez", Mexico City 14269, Mexico.
Sleep is a vital biological function governed by neuronal networks in the brainstem, hypothalamus, and thalamus. Disruptions in these circuits contribute to the sleep disturbances observed in neurodegenerative disorders, including Parkinson's disease, epilepsy, Huntington's disease, and Alzheimer's disease. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and abnormal protein accumulation adversely affect sleep architecture in these conditions.
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