Invited Review CALL FOR PAPERS Physiology and Pharmacology of Temperature Regulation The dorsomedial hypothalamus: a new player in thermoregulation

id 13940&is_tech 0] 49. DiMicco JA, Soltis RP, Anderson JJ, and Wible JH Jr. Hypothalamic mechanisms and the cardiovascular response to stress. In: Central Neural Mechanisms in Cardiovascular Regulation, vol. II, edited by Kunos G and Ciriello J, Boston, MA: Birkhauser, 1992, p. 52–80. 50. DiMicco JA, Samuels BC, Zaretskaia MV, and Zaretsky DV. The dorsomedial hypothalamus and the response to stress: part renaissance, part revolution. Pharmacol Biochem Behav 71: 469–480, 2002. 51. DiMicco JA, Sarkar S, Zaretskaia MV, and Zaretsky DV. Stressinduced cardiac stimulation and fever: Common hypothalamic origins and brainstem mechanisms. Auton Neurosci Basic Clin 126–127: 106– 119, 2006. 52. Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis 179 Suppl 2: S294–S304, 1999. 53. Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res 10: 201–222, 2004. 54. Elias CF, Kelly JF, Lee CE, Ahima RS, Drucker DJ, Saper CB, and Elmquist JK. Chemical characterization of leptin-activated neurons in the rat brain. J Comp Neurol 423: 261–281, 2000. 55. Elmquist JK and Saper CB. Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide. J Comp Neurol 374: 315–331, 1996. 56. Elmquist JK, Scammell TE, Jacobson CD, and Saper CB. Distribution of Fos-like immunoreactivity in the rat brain following intravenous lipopolysaccharide administration. J Comp Neurol 371: 85–103, 1996. 57. Elmquist JK, Scammell TE, and Saper CB. Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends Neurosci 20: 565–570, 1997. 58. Engelmann M, Landgraf R, and Wotjak CT. The hypothalamicneurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: an old concept revisited. Front Neuroendocrinol 25: 132–149, 2004. 59. Falcon-Lesses M and Proger SH. Psychogenic fever. N Engl J Med 203: 1034–1036, 1930. 60. Ferreira-Netto C, Borelli KG, and Brandao ML. Neural segregation of Fos-protein distribution in the brain following freezing and escape behaviors induced by injections of either glutamate or NMDA into the dorsal periaqueductal gray of rats. Brain Res 1031: 151–163, 2005. 61. Freake HC and Oppenheimer JH. Thermogenesis and thyroid function. Annu Rev Nutr 15: 263–291, 1995. 62. Freeman PH and Wellman PJ. Brown adipose tissue thermogenesis induced by low level electrical stimulation of hypothalamus in rats. Brain Res Bull 18: 7–11, 1987. 63. Fregly MJ and Schechtman O. Direct blood pressure measurements in rats during abrupt exposure to, and removal from, cold air. Proc Soc Exp Biol Med 205: 119–123, 1994. 64. Fukuhara K, Kvetnansky R, Cizza G, Pacak K, Ohara H, Goldstein DS, and Kopin IJ. Interrelations between sympathoadrenal system and hypothalamo-pituitary-adrenocortical/thyroid systems in rats exposed to cold stress. J Neuroendocrinol 8: 533–541, 1996. 65. Fyda DM, Cooper KE, and Veale WL. Contribution of brown adipose tissue to central PGE1-evoked hyperthermia in rats. Am J Physiol Regul Integr Comp Physiol 260: R59–R66, 1991. 66. Gautron L, Mingam R, Moranis A, Combe C, and Laye S. Influence of feeding status on neuronal activity in the hypothalamus during lipopolysaccharide-induced anorexia in rats. Neuroscience 134: 933–946, 2005. 67. Geller EB, Hawk C, Keinath SH, Tallarida RJ, and Adler MW. Subclasses of opioids based on body temperature change in rats: acute subcutaneous administration. J Pharmacol Exp Ther 225: 391–398, 1983. 68. Goodchild AK, Dampney RA, and Bandler R. A method for evoking physiological responses by stimulation of cell bodies, but not axons of passage, within localized regions of the central nervous system. J Neurosci Methods 6: 351–363, 1982. 69. Gotsev T and Ivanov A. Psychogenic elevation of body temperature in healthy persons. Acta Physiol Hung 1: 53–62, 1950. 70. Hamilton CL and Ciaccia PJ. Hypothalamus, temperature regulation, and feeding in the rat. Am J Physiol 221: 800–807, 1971. 71. Halvorson I, Gregor L, and Thornhill JA. Brown adipose tissue thermogenesis is activated by electrical and chemical (L-glutamate) stimulation of the ventromedial hypothalamic nucleus in cold-acclimated rats. Brain Res 522: 76–82, 1990. 72. Halvorson I and Thornhill J. Posterior hypothalamic stimulation of anesthetized normothermic and hypothermic rats evokes shivering thermogenesis. Brain Res 610: 208–215, 1993. 73. Hasday JD, Fairchild KD, and Shanholtz C. The role of fever in the infected host. Microbes Infect 2: 1891–1904, 2000. 74. Hellstrom B. Heat vasodilatation of the rat tail. Can J Physiol Pharmacol 53: 202–206, 1975. 75. Hensel H. Neural processes in thermoregulation. Physiol Rev 53: 948– 1017, 1973. 76. Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, and Cullinan WE. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol 24: 151–180, 2003. 77. Hermann DM, Luppi PH, Peyron C, Hinckel P, and Jouvet M. Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars alpha demonstrated by iontophoretic application of choleratoxin (subunit b). J Chem Neuroanat 13: 1–21, 1997. 78. Hjorth S. Hypothermia in the rat induced by the potent serotoninergic agent 8-OH-DPAT. J Neural Trans Gen 61: 131–135, 1985. 79. Holt SJ, Wheal HV, and York DA. Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres. Brain Res 405: 227–233, 1987. 80. Hori T, Nakashima T, Koga H, Kiyohara T, and Inoue T. Convergence of thermal, osmotic and cardiovascular signals on preoptic and anterior hypothalamic neurons in the rat. Brain Res Bull 20: 879–885, 1988. 81. Horiuchi J, McAllen RM, Allen AM, Killinger S, Fontes MA, and Dampney RA. Descending vasomotor pathways from the dorsomedial hypothalamic nucleus: role of medullary raphe and RVLM. Am J Physiol Regul Integr Comp Physiol 287: R824–R832, 2004. 82. Horiuchi J, Wakabayashi S, and Dampney RA. Activation of 5-hydroxytryptamine 1A receptors suppresses the cardiovascular response evoked from the dorsomedial hypothalamic nucleus. Hypertension 46: 173–179, 2005. 83. Horn T, Wilkinson MF, Landgraf R, and Pittman QJ. Reduced febrile responses to pyrogens after lesions of the hypothalamic paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol 267: R323– R328, 1994. 84. Hosono M, Hiruma T, Watanabe K, Hayashi Y, Ohnishi H, Takata Y, and Kato H. Inhibitory effect of cilnidipine on pressor response to acute cold stress in spontaneously hypertensive rats. Jpn J Pharmacol 69: 119–125, 1995. 85. Hosoya Y. Hypothalamic projections to the ventral medulla oblongata in the rat, with special reference to the nucleus raphe pallidus: a study using autoradiographic and HRP techniques. Brain Res 344: 338–350, 1985. 86. Hosoya Y, Ito R, and Kohno K. The topographical organization of neurons in the dorsal hypothalamic area that project to the spinal cord or to the nucleus raphe pallidus in the rat. Exp Brain Res 66: 500–506, 1987. Invited Review R60 THE DORSOMEDIAL HYPOTHALAMUS AND THERMOREGULATION AJP-Regul Integr Comp Physiol • VOL 292 • JANUARY 2007 • www.ajpregu.org by 10.0.33.1 on A uust 5, 2017 http://ajpphysiology.org/ D ow nladed fom 87. Hosoya Y, Sugiura Y, Zhang FZ, Ito R, and Kohno K. Direct projection from the dorsal hypothalamic area to the nucleus raphe pallidus: a study using anterograde transport with Phaseolus vulgaris leucoagglutinin in the rat. Exp Brain Res 75: 40–46, 1989. 88. Hugie T, Halvorson I, and Thornhill J. Brown adipose tissue temperature responses following electrical stimulation of ventromedial hypothalamic and lateral preoptic areas or after norepinephrine infusion to Long-Evans or Sprague-Dawley rats. Brain Res 575: 57–62, 1992. 89. Hunter WS. Anteroventral third ventricle lesion suppresses fever, but not stress-induced hyperthermia in rats. Ann NY Acad Sci 813: 420–426, 1997. 90. Imai-Matsumura K, Matsumura K, and Nakayama T. Involvement of ventromedial hypothalamus in brown adipose tissue thermogenesis induced by preoptic cooling in rats. Jpn J Physiol 34: 939–943, 1984. 91. Iwai M, Hell NS, and Shimazu T. Effect of ventromedial hypothalamic stimulation on blood flow of brown adipose tissue in rats. Pflügers Arch 410: 44–47, 1987. 92. Jepson MM, Millward DJ, Rothwell NJ, and Stock MJ. Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats. Am J Physiol Endocrinol Metab 255: E617–E620, 1988. 93. Kanosue K, Niwa K, Andrew PD, Yasuda H, Yanase M, Tanaka H, and Matsumura K. Lateral distribution of hypothalamic signals controlling thermoregulatory vasomotor activity and shivering in rats. Am J Physiol Regul Integr Comp Physiol 260: R486–R493, 1991. 94. Kanosue K, Zhang YH, Yanase-Fujiwara M, and Hosono T. Hypothalamic network for thermoregulatory shivering. Am J Physiol Regul Integr Comp Physiol 267: R275–R282, 1994. 95. Kelly L and Bielajew C. Ventromedial hypothalamic regulation of brown adipose tissue. Neuroreport 2: 41–44, 1991. 96. Kerman IA, Akil H, and Watson SJ. Rostral elements of sympathomotor circuitry: a virally mediated transsynaptic tracing study. J Neurosci 26: 3423–3433, 2006. 97. Kishi E, Ootsuka Y, and Terui N. Different cardiovascular neuron groups in the ventral reticular formation of the rostral medulla in rabbits: single neurone studies. J Auton Nerv Syst 79:74–83, 2000. 98. Kiyohara T, Miyata S, Nakamura T, Shido O, Nakashima T, and Shibata M. Differences in Fos expression in the rat brains between cold and warm ambient exposures. Brain Res Bull 38: 193–201, 1995. 99. Kluger MJ, Gonzalez RR, and Hardy JD. Peripheral thermal sensitivity in the rabbit. Am J Physiol 222: 1031–1034, 1972. 100. Kluger MJ, O’Reilly B, Shope TR, and Vander AJ. Further evidence that stress hyperthermia is a fever. Physiol Behav 39: 763–766, 1987. 101. Kobayashi A, Osaka T, Namba Y, Inoue S, and Kimura S. CGRP microinjection into the ventromedial or dorsomedial hypothalamic nucleus activates heat production. Brain Res 827: 176–184, 1999. 102. Kozak W, Kluger MJ, Tesfaigzi J, Kozak A, Mayfield KP, Wachulec M, and Dokladny K. Molecular mechanisms of fever and endogenous antipyresis. Ann NY Acad Sci 917: 121–134, 2000. 103. Lacroix S and Rivest S. Functional circuitry in the brain of immunechallenged rats: partial involvement of prostaglandins. J Comp Neurol 387: 307–324, 1997. 104. Laflamme N, Feuvrier E, Richard D, and Rivest S. Involvement of serotonergic pathways in mediating the neuronal activity and genetic transcription of neuroendocrine corticotropin-releasing factor in the brain of systemically endotoxin-challenged rats. Neuroscience 88: 223–240, 1999. 105. Landsberg L, Saville ME, and Young JB. Sympathoadrenal system and regulation of thermogenesis. Am J Physiol Endocrinol Metab 247: E181–E189, 1984. 106. Laurberg P, Andersen S, and Karmisholt J. Cold adaptation and thyroid hormone metabolism. Horm Metab Res 37: 545–549, 2005. 107. Lecci A, Borsini F, Mancinelli A, D’Aranno V, Stasi MA, Volterra G, and Meli A. Effect of serotoninergic drugs on stress-induced hyperthermia (SIH) in mice. J Neural Trans Gen 82: 219–230, 1990. 108. Leppaluoto J, Paakkonen T, Korhonen I, and Hassi J. Pituitary and autonomic responses to cold exposures in man. Acta Physiol Scand 184: 255–264, 2005. 109. Levin BE, Dunn-Meynell AA, Ricci MR, and Cummings DE. Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. Am J Physiol Endocrinol Metab 285: E949–E957, 2003. 110. Li HY and Sawchenko PE. Hypothalamic effector neurons and extended circuitries activated in “neurogenic” stress: a comparison of footshock effects exerted acutely, chronically, and in animals with controlled glucocorticoid levels. J Comp Neurol 393: 244–266, 1998. 111. Lipski J, Bellingham MC, West MJ, and Pilowsky P. Limitations of the technique of pressure microinjection of excitatory amino acids for evoking responses from localized regions of the CNS. J Neurosci Methods 26: 169–179, 1988. 112. Lipton JM and Clark WG. Neurotransmitters in temperature control. Annu Rev Physiol 48: 613–623, 1986. 113. Long NC, Vander AJ, Kunkel SL, and Kluger MJ. Antiserum against tumor necrosis factor increases stress hyperthermia in rats. Am J Physiol Regul Integr Comp Physiol 258: R591–R595, 1990. 114. Long NC, Morimoto A, Nakamori T, Yamashiro O, and Murakami N. Intraperitoneal injections of prostaglandin E2 attenuate hyperthermia induced by restraint or interleukin-1 in rats. J Physiol 444: 363–373, 1991. 115. Mackowiak PA. Concepts of fever. Arch Intern Med 158: 1870–1881, 1998. 116. Madden CJ and Morrison SF. Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 286: R320–R325, 2004. 117. Marsh AJ, Fontes MA, Killinger S, Pawlak DB, Polson JW, and Dampney RA. Cardiovascular responses evoked by leptin acting on neurons in the ventromedial and dorsomedial hypothalamus. Hypertension 42: 488–493, 2003. 118. Maruyama M, Nishi M, Konishi M, Takashige Y, Nagashima K, Kiyohara T, and Kanosue K. Brain regions expressing Fos during thermoregulatory behavior in rats. Am J Physiol Regul Integr Comp Physiol 285: R1116–R1123, 2003. 119. McKitrick DJ. Expression of fos in the hypothalamus of rats exposed to warm and cold temperatures. Brain Res Bull 53: 307–315, 2000. 120. Mercer JG, Hoggard N, Williams LM, Lawrence CB, Hannah LT, and Trayhurn P. Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett 387: 113–116, 1996. 121. Mihaly E, Fekete C, Legradi G, and Lechan RM. Hypothalamic dorsomedial nucleus neurons innervate thyrotropin-releasing hormonesynthesizing neurons in the paraventricular nucleus. Brain Res 891: 20–31, 2001. 122. Millan MJ, Rivet JM, Canton H, Le Marouille-Girardon S., and Gobert A. Induction of hypothermia as a model of 5-hydroxytryptamine1A receptor-mediated activity in the rat: a pharmacological characterization of the actions of novel agonists and antagonists. J Pharmacol Exp Ther 264: 1364–1376, 1993. 123. Monda M, Amaro S, Sullo A, and De Luca B. Injection of muscimol in the posterior hypothalamus reduces the PGE1-hyperthermia in the rat. Brain Res Bull 37: 575–580, 1995. 124. Monda M, Sullo A, De Luca V, and Viggiano A. Ibotenate lesion of the ventromedial hypothalamus lowers hyperthermic effects of prostaglandin E1. Physiol Res 50: 321–326, 2001. 125. Moran MM, Roy RR, Wade CE, Corbin BJ, and Grindeland RE. Size constraints of telemeters in rats. J Appl Physiol 85: 1564–1571, 1998. 126. Morimoto A, Murakami N, Ono T, Watanabe T, and Sakata Y. Stimulation of ventromedial hypothalamus induces cold defense responses in conscious rabbits. Am J Physiol Regul Integr Comp Physiol 250: R560–R566, 1986. 127. Morin SM, Stotz-Potter EH, and DiMicco JA. Injection of muscimol in dorsomedial hypothalamus and stress-induced Fos expression in paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol 280: R1276–R1284, 2001. 128. Morrison SF. RVLM and raphe differentially regulate sympathetic outflows to splanchnic and brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 276: R962–R973, 1999. 129. Morrison SF. Differential regulation of brown adipose and splanchnic sympathetic outflows in rat: roles of raphe and rostral ventrolateral medulla neurons. Clin Exp Pharmacol Physiol 28: 138–43, 2001. 130. Morrison SF. Raphe pallidus neurons mediate prostaglandin E2-evoked increases in brown adipose tissue thermogenesis. Neuroscience 121: 17–24, 2003. 131. Morrison SF. Activation of 5-HT1A receptors in raphe pallidus inhibits leptin-evoked increases in brown adipose tissue thermogenesis. Am J Physiol Regul Integr Comp Physiol 286: R832–R837, 2004. 132. Morrison SF, Sved AF, and Passerin AM. GABA-mediated inhibition of raphe pallidus neurons regulates sympathetic outflow to brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 276: R290–R297, 1999. Invited Review R61 THE DORSOMEDIAL HYPOTHALAMUS AND THERMOREGULATION AJP-Regul Integr Comp Physiol • VOL 292 • JANUARY 2007 • www.ajpregu.org by 10.0.33.1 on A uust 5, 2017 http://ajpphysiology.org/ D ow nladed fom 133. Mory G, Ricquier D, Nechad M, and Hemon P. Impairment of trophic response of brown fat to cold in guanethidine-treated rats. Am J Physiol Cell Physiol 242: C159–C165, 1982. 134. Muchlinski AE, Baldwin BC, Padick DA, Lee BY, Salguero HS, and Gramajo R. California ground squirrel body temperature regulation patterns measured in the laboratory and in the natural environment. Comp Biochem Physiol A 120: 365–372, 1998. 135. Nagashima K, Nakai S, Tanaka M, and Kanosue K. Neuronal circuitries involved in thermoregulation. Auton Neurosci Basic Clin 85: 18–25, 2000. 136. Nakamura K, Matsumura K, Kaneko T, Kobayashi S, Katoh H, and Negishi M. The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area. J Neurosci 22: 4600–4610, 2002. 137. Nakamura K, Matsumura K, Hubschle T, Nakamura Y, Hioki H, Fujiyama F, Boldogkoi Z, Konig M, Thiel HJ, Gerstberger R, Kobayashi S, and Kaneko T. Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions. J Neurosci 24: 5370–5380, 2004. 138. Nakamura Y, Nakamura K, Matsumura K, Kobayashi S, Kaneko T, and Morrison SF. Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus. Eur J Neurosci 22: 3137–3146, 2005. 139. Nalivaiko E and Blessing WW. Raphe region mediates changes in cutaneous vascular tone elicited by stimulation of amygdala and hypothalamus in rabbits. Brain Res 891: 130–137, 2001. 140. Nalivaiko E, Ootsuka Y, and Blessing WW. Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits. Am J Physiol Regul Integr Comp Physiol 289: R596–R604, 2005. 141. Nason MW Jr and Mason P. Medullary raphe neurons facilitate brown adipose tissue activation. J Neurosci 26: 1190–1198, 2006. 142. Niijima A, Rohner-Jeanrenaud F, and Jeanrenaud B. Role of ventromedial hypothalamus on sympathetic efferents of brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 247: R650–R654, 1984. 143. Nogueira MI, de Rezende BD, do Vale LE, and Bittencourt JC. Afferent connections of the caudal raphe pallidus nucleus in rats: a study using the fluorescent retrograde tracers fluorogold and true-blue. Annu Anat 182: 35–45, 2000. 144. Oka K, Oka T, and Hori T. Prostaglandin E2 may induce hyperthermia through EP1 receptor in the anterior wall of the third ventricle and neighboring preoptic regions. Brain Res 767: 92–99, 1997. 145. Oka T, Oka K, and Hori T. Mechanisms and mediators of psychological stress-induced rise in core temperature. Psychosom Med 63: 476– 486, 2001. 146. Okamura H, Abitbol M, Julien JF, Dumas S, Berod A, Geffard M, Kitahama K, Bobillier P, Mallet J, and Wiklund L. Neurons containing messenger RNA encoding glutamate decarboxylase in rat hypothalamus demonstrated by in situ hybridization, with special emphasis on cell groups in medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus. Neuroscience 39: 675–699, 1990. 147. Oldfield BJ, Giles ME, Watson A, Anderson C, Colvill LM, and McKinley MJ. The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat. Neuroscience 110: 515–526, 2002. 148. Ootsuka Y, Rong W, Kishi E, Koganezawa T, and Terui N. Rhythmic activities of the sympatho-excitatory neurons in the medulla of rabbits: neurons controlling cutaneous vasomotion. Auton Neurosci Basic Clin 101: 48–59, 2002. 149. Ootsuka Y, Blessing WW, and McAllen RM. Inhibition of rostral medullary raphe neurons prevents cold-induced activity in sympathetic nerves to rat tail and rabbit ear arteries. Neurosci Lett 357: 58–62, 2004. 150. Ootsuka Y and Blessing WW. Inhibition of medullary raphe/parapyramidal neurons prevents cutaneous vasoconstriction elicited by alerting stimuli and by cold exposure in conscious rabbits. Brain Res 1051: 189–193, 2005. 151. Ootsuka Y and McAllen RM. Interactive drives from two brain stem premotor nuclei are essential to support rat tail sympathetic activity. Am J Physiol Regul Integr Comp Physiol 289: R1107–R1115, 2005. 152. Owens NC, Ootsuka Y, Kanosue K, and McAllen RM. Thermoregulatory control of sympathetic fibres supplying the rat’s tail. J Physiol 543:849–858, 2002. 153. Palma BD, Suchecki D, and Tufik S. Differential effects of acute cold and footshock on the sleep of rats. Brain Res 861: 97–104, 2000. 154. Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates. New York: Academic Press, 1998. 155. Pellegrino LJ, Pellegrino AS, and Cushman AJ. A Stereotaxic Atlas of the Rat Brain. New York: Plenum, 1979. 156. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, and Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540–543, 1995. 157. Perkins MN, Rothwell NJ, Stock MJ, and Stone TW. Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 289:401–402, 1981. 158. Ranck JB Jr. Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98: 417–440, 1975. 159. Rand RP, Burton AC, and Ing T. The tail of the rat in temperature regulation and acclimatization. Can J Physiol Pharmacol 43:257–267, 1964. 160. Rathner JA and McAllen RM. Differential control of sympathetic drive to the rat tail artery and kidney by medullary premotor cell groups. Brain Res 834: 196–199, 1999. 161. Rathner JA, Owens NC, and McAllen RM. Cold-activated raphespinal neurons in rats. J Physiol 535: 841–854, 2001. 162. Renbourn ET. Body temperature and pulse rate in boys and young men prior to sporting contests. A study of emotional hyperthermia with a review of the literature. J Psychosom Res 4: 149–175, 1960. 163. Rezvani AH, Gordon CJ, and Heath JE. Action of preoptic injections of beta-endorphin on temperature regulation in rabbits. Am J Physiol Regul Integr Comp Physiol 243: R104–R111, 1982. 164. Ricquier D, Mory G, and Hemon P. Changes induced by cold adaptation in the brown adipose tissue from several species of rodents, with special reference to the mitochondrial components. Can J Biochem 57: 1262–1266, 1979. 165. Rivest S and Laflamme N. Neuronal activity and neuropeptide gene transcription in the brains of immune-challenged rats. J Neuroendocrinol 7: 501–525, 1995. 166. Romanovsky AA, Kulchitsky VA, Simons CT, and Sugimoto N. Methodology of fever research: why are polyphasic fevers often thought to be biphasic? Am J Physiol Regul Integr Comp Physiol 275: R332– R338, 1998. 167. Romanovsky AA. Do fever and anapyrexia exist? Analysis of set point-based definitions. Am J Physiol Regul Integr Comp Physiol 287: R992–R995, 2004. 168. Romanovsky AA. Signaling the brain in the early sickness syndrome: are sensory nerves involved? Front Biosci 9: 494–504, 2004. 169. Rothwell NJ and Stock MJ. Diet-induced thermogenesis. Adv Nutr Res 5: 201–220, 1983. 170. Sagar SM, Price KJ, Kasting NW, and Sharp FR. Anatomic patterns of Fos immunostaining in rat brain following systemic endotoxin administration. Brain Res Bull 36: 381–392, 1995. 171. Saito M, Minokoshi Y, and Shimazu T. Ventromedial hypothalamic stimulation accelerates norepinephrine turnover in brown adipose tissue of rats. Life Sci 41: 193–197, 1987. 172. Samuels BC, Zaretsky DV, and DiMicco JA. Tachycardia evoked by disinhibition of the dorsomedial hypothalamus is mediated through medullary raphe. J Physiol 538: 941–946, 2002. 173. Samuels BC, Zaretsky DV, and DiMicco JA. Dorsomedial hypothalamic sites where disinhibition evokes tachycardia correlate with location of raphe-projecting neurons in rats. Am J Physiol Regul Integr Comp Physiol 287: R472–R478, 2004. 174. Sarkar S, Zaretskaia MV, Zaretsky DV, and DiMicco JA. Hypothalamic neurons projecting to raphe pallidus: NOS and stress-induced fos expression (Abstract). Proc Ann Mtg Soc Neurosci, 183.21 2005. [The abstract is available at: http://sfn.scholarone.com/itin2005/main.html?is available at: http://sfn.scholarone.com/itin2005/main.html? new_page_id 126&abstract_id 15127&p_num 183.21&is_tech 0] 175. Sawchenko PE, Imaki T, Potter E, Kovacs K, Imaki J, and Vale W. The functional neuroanatomy of corticotropin-releasing factor. Ciba Fdn Sympos 172: 5–21; discussion 21–9, 1993. 176. Scholz H. Fever. J Physiol 284: R913–R915, 2003. 177. Sharkawi M. Morphine hyperthermia in the rat: its attenuation by physostigmine. Br J Pharmacol 44: 544–548, 1972. 178. Shen Z, Yanase M, Kanosue K, and Nakayama T. Effect of periaqueductal morphine injection on thermal response in rats. Jpn J Physiol 36: 485–496, 1986. 179. Shibata H and Nagasaka T. Contribution of nonshivering thermogenesis to stress-induced hyperthermia in rats. Jpn J Physiol 32: 991–995, 1982. 180. Simon E, Pierau FK, and Taylor DCM. Central and peripheral thermal control of effectors in homeothermic temperature regulation. Physiol Rev 66: 235–300, 1986. Invited Review R62 THE DORSOMEDIAL HYPOTHALAMUS AND THERMOREGULATION AJP-Regul Integr Comp Physiol • VOL 292 • JANUARY 2007 • www.ajpregu.org by 10.0.33.1 on A uust 5, 2017 http://ajpphysiology.org/ D ow nladed fom 181. Simon C, Gronfier C, Schlienger JL, and Brandenberger G. Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: relationship to sleep and body temperature. J Clin Endocrinol Metab 83: 1893–1899, 1998. 182. Singh ME, Verty AN, Price I, McGregor IS, and Mallet PE. Modulation of morphine-induced Fos-immunoreactivity by the cannabinoid receptor antagonist SR 141716. Neuropharmacology 47: 1157–1169, 2004. 183. Smith JE, Jansen AS, Gilbey MP, and Loewy AD. CNS cell groups projecting to sympathetic outflow of tail artery: neural circuits involved in heat loss in the rat. Brain Res 786: 153–164, 1998. 184. Soltis RP and DiMicco JA. GABAA and excitatory amino acid receptors in dorsomedial hypothalamus and heart rate in rats. Am J Physiol Regul Integr Comp Physiol 260: R13–R20, 1991. 185. Soltis RP and DiMicco JA. Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia. Am J Physiol Regul Integr Comp Physiol 262: R689–R697, 1992. 186. Song CK, Enquist LW, and Bartness TJ. New developments in tracing neural circuits with herpesviruses. Virus Res 111: 235–249, 2005. 187. Stehling O, Doring H, Ertl J, Preibisch G, and Schmidt I. Leptin reduces juvenile fat stores by altering the circadian cycle of energy expenditure. Am J Physiol Regul Integr Comp Physiol 271: R1770– R1774, 1996. 188. Stehling O, Doring H, Nuesslein-Hildesheim B, Olbort M, and Schmidt I. Leptin does not reduce body fat content but augments cold defense abilities in thermoneutrally reared rat pups. Pflügers Arch 434: 694–697, 1997. 189. Steiner AA, Rudaya AY, Robbins JR, Dragic AS, Langenbach R, and Romanovsky AA. Expanding the febrigenic role of cyclooxygenase-2 to the previously overlooked responses. Am J Physiol Regul Integr Comp Physiol 289: R1253–R1257, 2005. 190. Stocks JM, Taylor NA, Tipton MJ, and Greenleaf JE. Human physiological responses to cold exposure. Aviat Space Environ Med 75: 444–457, 2004. 191. Stotz-Potter EH, Willis LR, and DiMicco JA. Muscimol acts in dorsomedial and not paraventricular hypothalamic nucleus to suppress cardiovascular effects of stress. J Neurosci 16: 1173–1179, 1996. 192. Stotz-Potter EH, Morin SM, and DiMicco JA. Effect of microinjection of muscimol into the dorsomedial or paraventricular hyppothalamic nucleus on air stress-induced neuroendocrine and cardiovascular changes in rats. Brain Res 742: 219–224, 1996. 193. Stricker EM and Hainsworth FR. Thermolytic responses of rats in the heat. J Physiol 63: 430–433, 1971. 194. Sun Z, Cade JR, Fregly MJ, and Rowland NE. Effect of chronic treatment with propranolol on the cardiovascular responses to chronic cold exposure. Physiol Behav 62: 379–384, 1997. 195. Tanaka M, Tonouchi M, Hosono T, Nagashima K, Yanase-Fujiwara M, and Kanosue K. Hypothalamic region facilitating shivering in rats. Jpn J Physiol 51: 625–629, 2001. 196. Tanaka M, Nagashima K, McAllen RM, and Kanosue K. Role of the medullary raphe in thermoregulatory vasomotor control in rats. J Physiol 540: 657–664, 2002. 197. Tanaka M, Owens NC, Nagashima K, Kanosue K, and McAllen RM. Reflex activation of rat fusimotor neurons by body surface cooling, and its dependence on the medullary raphe. J Physiol 572: 569–583, 2006. 198. Taylor WF, DiCarlo SE, and Bishop VS. Neurogenic vasodilator control of rabbit ear blood flow. Am J Physiol Regul Integr Comp Physiol 262: R766–R770, 1992. 199. Taylor NC, Li A, and Nattie EE. Medullary serotonergic neurones modulate the ventilatory response to hypercapnia, but not hypoxia in conscious rats. J Physiol 566: 543–557, 2005. 200. ter Horst GJ and Luiten PG. The projections of the dorsomedial hypothalamic nucleus in the rat. Brain Res Bull 16: 231–248, 1986. 201. Thompson RH, Canteras NS, and Swanson LW. Organization of projections from the dorsomedial nucleus of the hypothalamus: A PHA-L study in the rat. J Comp Neurol 376: 143–173, 1996. 202. Thompson RH and Swanson LW. Organization of inputs to the dorsomedial nucleus of the hypothalamus: a reexamination with Fluorogold and PHAL in the rat. Brain Res Brain Res Rev 27: 89–118, 1998. 203. Thornhill JA and Halvorson I. Electrical stimulation of the posterior and ventromedial hypothalamic nuclei causes specific activation of shivering and nonshivering thermogenesis. Can J Physiol Pharmacol 72: 89–96, 1994. 204. Thornhill J, Jugnauth A, and Halvorson I. Brown adipose tissue thermogenesis evoked by medial preoptic stimulation is mediated via the ventromedial hypothalamic nucleus. Can J Physiol Pharmacol 72: 1042– 1048, 1994. 205. Tseng LF, Wei ET, Loh HH, and Li CH. Beta-endorphin: central sites of analgesia, catalepsy and body temperature changes in rats. J Pharmacol Exp Ther 214: 328–332, 1980. 206. Usategui R, Gillioz P, and Oliver C. Effect of cold exposure on alpha-MSH and ACTH release in the rat. Horm Metab Res 9: 519, 1977. 207. Van Ree JM, Spaapen-Kok WB, and de Weid D. Differential localization of pituitary-adrenal activation and temperature changes following intrahypothalamic microinjection of morphine in rats. Neuroendocrinology 22: 318–324, 1976. 208. Vellucci SV and Parrott RF. Prostaglandin-dependent c-Fos expression in the median preoptic nucleus of pigs subjected to restraint: correlation with hyperthermia. Neurosci Lett 198: 49–51, 1995. 209. Vollmer RR, Baruchin A, Kolibal-Pegher SS, Corey SP, Stricker EM, and Kaplan BB. Selective activation of norepinephrineand epinephrine-secreting chromaffin cells in rat adrenal medulla. Am J Physiol Regul Integr Comp Physiol 263: R716–R721, 1992. 210. von Euler C. Physiology and pharmacology of temperature regulation. Pharmacol Rev 13: 361–398, 1961. 211. Widdowson PS, Griffiths EC, and Slater P. Body temperature effects of opioids administered into the periaqueductal grey area of rat brain. Regul Pept 7: 259–267, 1983. 212. Woods AJ and Stock MJ. Biphasic brown fat temperature responses to hypothalamic stimulation in rats. Am J Physiol Regul Integr Comp Physiol 266: R328–R337, 1994. 213. Woods AJ and Stock MJ. Inhibition of brown fat activity during hypothalamic stimulation in the rat. Am J Physiol Regul Integr Comp Physiol 270: R605–R613, 1996. 214. Xin L, Geller EB, and Adler MW. Body temperature and analgesic effects of selective mu and kappa opioid receptor agonists microdialyzed into rat brain. J Pharmacol Exp Ther 281: 499–507, 1997. 215. Yoshida T and Bray GA. Catecholamine turnover in rats with ventromedial hypothalamic lesions. Am J Physiol Regul Integr Comp Physiol 246: R558–R565, 1984. 216. Yoshida K, Maruyama M, Hosono T, Nagashima K, Fukuda Y, Gerstberger R, and Kanosue K. Fos expression induced by warming the preoptic area in rats. Brain Res 933: 109–117, 2002. 217. Yoshida K, Nakamura K, Matsumura K, Kanosue K, Konig M, Thiel HJ, Boldogkoi Z, Toth I, Roth J, Gerstberger R, and Hubschle T. Neurons of the rat preoptic area and the raphe pallidus nucleus innervating the brown adipose tissue express the prostaglandin E receptor subtype EP3. Eur J Neurosci 18: 1848–1860, 2003. 218. Yoshida K, Konishi M, Nagashima K, Saper CB, and Kanosue K. Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter. Neuroscience 133: 1039– 1046, 2005. 219. Yoshimatsu H, Egawa M, and Bray GA. Sympathetic nerve activity after discrete hypothalamic injections of L-glutamate. Brain Res 601: 121–128, 1993. 220. Zabawska J, Lai H, and Horita A. Neural mechanisms mediating the hyperthermia elicited by prostaglandin E2 injected into the preopticanterior hypothalamus. Eur J Pharmacol 142: 9–16, 1987. 221. Zaretskaia MV, Zaretsky DV, Shekhar A, and DiMicco JA. Chemical Stimulation of the dorsomedial hypothalamus evokes non-shivering thermogenesis in anesthetized rats. Brain Res 928: 113–125, 2002. 222. Zaretskaia MV, Zaretsky DV, and DiMicco JA. Role of the dorsomedial hypothalamus in thermogenesis and tachycardia caused by microinjection of prostaglandin E2 into the preoptic area in anesthetized rats. Neurosci Lett 340: 1–4, 2003. 223. Zaretsky DV, Zaretskaia MV, Samuels BC, Cluxton LK, and DiMicco JA. Microinjection of muscimol into raphe pallidus suppresses tachycardia associated with air stress in conscious rats. J Physiol 546: 243–250, 2003. 224. Zhang YH, Lu J, Elmquist JK, and Saper CB. Lipopolysaccharide activates specific populations of hypothalamic and brainstem neurons that project to the spinal cord. J Neurosci 20: 6578–6586, 2000. Invited Review R63 THE DORSOMEDIAL HYPOTHALAMUS AND THERMOREGULATION AJP-Regul Integr Comp Physiol • VOL 292 • JANUARY 2007 • www.ajpregu.org by 10.0.33.1 on A uust 5, 2017 http://ajpphysiology.org/ D ow nladed fom