Neurons in the paraventricular nucleus of the hypothalamus inhibit sympathetic outflow to brown adipose tissue

Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon Submitted 15 December 2008 ; accepted in final form 5 January 2009 The paraventricular nucleus of the hypothalamus (PVH) plays an important role in energy homeostasis, regulating neuroendocrine, behavioral, and autonomic functions. However, the role of the PVH in regulating thermogenesis and energy expenditure in brown adipose tissue (BAT) is unclear. The present study investigated the effect of activating neurons within the PVH on BAT thermogenesis. In urethane- and chloralose-anesthetized, artificially ventilated rats maintained at a core body temperature of 37.0–38.0°C, microinjection of N -methyl- D -aspartate (NMDA, 12 pmol in 60 nl) in the PVH did not increase BAT sympathetic nerve activity (SNA) or BAT thermogenesis. In contrast, the increase in BAT SNA evoked by body cooling was completely reversed by microinjection of NMDA in the PVH. Additionally, the increases in BAT SNA evoked by body cooling, by microinjection of prostaglandin E 2 (170 pmol in 60 nl) in the medial preoptic area or by microinjection of bicuculline (30 pmol in 60 nl) in the dorsomedial hypothalamus were completely reversed by microinjection of bicuculline (30 pmol in 60 nl) in the PVH. Although the increases in BAT SNA and thermogenesis evoked by microinjection of NMDA (12 pmol in 60 nl) in the raphe pallidus (RPa) was markedly attenuated following microinjection of bicuculline (30 pmol) in the PVH, the increases in BAT SNA and thermogenesis evoked by microinjection of bicuculline (30 pmol in 60 nl) in the RPa were unaffected by microinjection of bicuculline in the PVH. These results demonstrate that disinhibition of neurons in the PVH inhibits BAT SNA likely via activation of a GABAergic input to BAT sympathetic premotor neurons in the RPa. thermoregulation; sympathetic premotor neurons; raphe; paraventricular nucleus; metabolism Address for reprint requests and other correspondence: C. J. Madden, Oregon National Primate Research Center/OHSU, 505 NW 185th Ave., Beaverton, OR 97006 (e-mail: maddench{at}ohsu.edu )