Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms

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Abstract
The suprachiasmatic nucleus (SCN) contains the brain's circadian pacemaker, but mechanisms by which it controls circadian rhythms of sleep and related behaviors are poorly understood. Previous anatomic evidence has implicated the dorsomedial hypothalamic nucleus (DMH) in circadian control of sleep, but this hypothesis remains untested. We now show that excitotoxic lesions of the DMH reduce circadian rhythms of wakefulness, feeding, locomotor activity, and serum corticosteroid levels by 78-89% while also reducing their overall daily levels. We also show that the DMH receives both direct and indirect SCN inputs and sends a mainly GABAergic projection to the sleep-promoting ventrolateral preoptic nucleus, and a mainly glutamate-thyrotropin-releasing hormone projection to the wake-promoting lateral hypothalamic area, including orexin (hypocretin) neurons. Through these pathways, the DMH may influence a wide range of behavioral circadian rhythms.