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The Journal of Neuroscience, January 25, 2006, 26(4):1190-1198; doi:10.1523/JNEUROSCI.4707-05.2006

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Behavioral/Systems/Cognitive
Medullary Raphe Neurons Facilitate Brown Adipose Tissue Activation

Malcolm W. Nason, Jr and Peggy Mason

Committee on Neurobiology and Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637

Correspondence should be addressed to Dr. Peggy Mason, Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, MC 0926, 947 East 58th Street, Chicago, IL 60637. Email: pmason{at}uchicago.edu

Recent evidence suggests that neurons in the medullary raphe are critical to the activation of brown adipose tissue (BAT), the major source of nonshivering heat production in the rat. Yet it is unclear which medullary raphe cells participate in cold defense and how participating cells contribute to BAT activation. Therefore, we recorded extracellularly from raphe cells during three thermoregulatory challenges that evoked an increase in BAT temperature in anesthetized rats: central cold, ambient cold, or intracerebroventricular prostaglandin E₂ (PGE₂) injection. Physiologically identified serotonergic (p5HT) cell discharge increased in response to cold or PGE₂ administration and was positively correlated with BAT temperature. However, none of the 147 physiologically identified non-serotonergic (non-p5HT) cells recorded responded to thermoregulatory challenges that evoked an increase in BAT temperature. To test for modulation of BAT activation by non-p5HT cells that are either excited (ON cells) or inhibited (OFF cells) by noxious cutaneous stimulation, noxious stimuli were applied during evoked BAT temperature increases. Noxious stimulation suppressed BAT activation, suggesting that cells inhibited by noxious stimulation facilitate spinal circuits controlling BAT. To test whether medullary OFF cells modulate BAT activity, the µ-opiate receptor agonist (D-Ala², N-Me-Phe⁴, Gly-ol⁵)-enkephalin (DAMGO) was microinjected into the raphe magnus, a manipulation that selectively activates OFF cells. DAMGO microinjection blocked noxious stimulation-evoked suppression of PGE₂-induced BAT temperature increases. Thus, both p5HT and non-p5HT OFF cells in the medullary raphe facilitate BAT activation in response to cold challenge or pyrogen.

Key words: ventromedial medulla; autonomic modulation; nociceptive modulation; raphe pallidus; raphe magnus; thermoregulation

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Received Aug. 24, 2005; revised Dec. 7, 2005; accepted Dec. 7, 2005.

Correspondence should be addressed to Dr. Peggy Mason, Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, MC 0926, 947 East 58th Street, Chicago, IL 60637. Email: pmason{at}uchicago.edu

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