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Am J Physiol Regul Integr Comp Physiol 292: R47-R63, 2007. First published September 7, 2006; doi:10.1152/ajpregu.00498.2006
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INVITED REVIEW

CALL FOR PAPERS
Physiology and Pharmacology of Temperature Regulation

The dorsomedial hypothalamus: a new player in thermoregulation

Joseph A. DiMicco and Dmitry V. Zaretsky

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 14 July 2006 ; accepted in final form 1 September 2006

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 brain stem, 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 least significant difference 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 microinjection of PGE2 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 nonshivering 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.

brown fat; sympathetic nervous system; body temperature; fever; raphe pallidus



Address for reprint requests and other correspondence: J. A. DiMicco, Indiana Univ. School of Medicine, Dept. of Pharmacology and Toxicology, 635 Barnhill Dr., Rm. MS A417, Indianapolis, IN 46202 (e-mail: jdimicco{at}iupui.edu)




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