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1 Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States
* To whom correspondence should be addressed. E-mail: jdimicco{at}iupui.edu.
Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological responses to exteroceptive ("emotional") stress in rats, including tachycardia. Tachycardia evoked from the DMH or seen in experimental stress in rats is blocked by microinjection of the GABAA receptor agonist muscimol into the rostral raphe pallidus (rRP), an important thermoregulatory site in the brainstem where disinhibition elicits sympathetically-mediated activation of brown adipose tissue (BAT) and cutaneous vasoconstriction in the tail. Disinhibition of neurons in the DMH also elevates core temperature in conscious rats, and sympathetic activity to interscapular BAT (IBAT) and IBAT temperature in anesthetized preparations. The latter effects are blocked by microinjection of muscimol into the rRP, while microinjection of muscimol into either the rRP or DMH suppresses increases in sympathetic nerve activity to IBAT, IBAT temperature, and core body temperature elicited either by either microinjection of prostaglandin E2 into the preoptic area (an experimental model for fever), or central administration of fentanyl. Neurons concentrated in the dorsal region of the DMH project directly to the rRP, a location corresponding to that of neurons transsynaptically labeled from IBAT. Thus, these neurons control non-shivering thermogenesis in rats, and their activation signals its recruitment in diverse experimental paradigms. Evidence also points to a role for neurons in the DMH in thermoregulatory cutaneous vasoconstriction, shivering, and endocrine adjustments. These directions provide intriguing avenues for future exploration that may expand our understanding of the DMH as an important hypothalamic site for the integration of autonomic, endocrine, and behavioral responses to diverse challenges.
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