A thermosensory pathway mediating heat-defense responses

Afferent neural transmission of temperature sensation from skin thermoreceptors to the central thermoregulatory system is important for the defense of body temperature against environmental thermal challenges. Here, we report a thermosensory pathway that triggers physiological heat-defense responses to elevated environmental temperature. Using in vivo electrophysiological and anatomical approaches in the rat, we found that neurons in the dorsal part of the lateral parabrachial nucleus (LPBd) glutamatergically transmit cutaneous warm signals from spinal somatosensory neurons directly to the thermoregulatory command center, the preoptic area (POA). Intriguingly, these LPBd neurons are located adjacent to another group of neurons that mediate cutaneous cool signaling to the POA. Functional experiments revealed that this LPBd–POA warm sensory pathway is required to elicit autonomic heat-defense responses, such as cutaneous vasodilation, to skin-warming challenges. These findings provide a fundamental framework for understanding the neural circuitry maintaining thermal homeostasis, which is critical to survive severe environmental temperatures.

[1]  R. Nahin,et al.  Spinal lamina I projection neurons in the rat: Collateral innervation of parabrachial area and thalamus , 1989, Neuroscience.

[2]  A. Craig,et al.  Quantitative response characteristics of thermoreceptive and nociceptive lamina I spinothalamic neurons in the cat. , 2001, Journal of neurophysiology.

[3]  A. Loewy,et al.  CNS cell groups projecting to sympathetic outflow of tail artery: neural circuits involved in heat loss in the rat , 1998, Brain Research.

[4]  S. Morrison,et al.  Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[5]  S. Morrison,et al.  Preoptic mechanism for cold‐defensive responses to skin cooling , 2008, The Journal of physiology.

[6]  S. K. Agarwal,et al.  Supramedullary inputs to cardiovascular neurons of rostral ventrolateral medulla in rats. , 1993, The American journal of physiology.

[7]  T. Osaka,et al.  Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[8]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[9]  Takeshi Kaneko,et al.  Identification of Sympathetic Premotor Neurons in Medullary Raphe Regions Mediating Fever and Other Thermoregulatory Functions , 2004, The Journal of Neuroscience.

[10]  T. Curran,et al.  Expression of c-fos protein in brain: metabolic mapping at the cellular level. , 1988, Science.

[11]  S. Morrison,et al.  Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions , 2009, Neuroscience.

[12]  H. Wanner,et al.  European Seasonal and Annual Temperature Variability, Trends, and Extremes Since 1500 , 2004, Science.

[13]  T. Nagasaka,et al.  Relationship between body core and peripheral temperatures at the onset of thermoregulatory responses in rats. , 1993, The Japanese journal of physiology.

[14]  Takeshi Kaneko,et al.  The Rostral Raphe Pallidus Nucleus Mediates Pyrogenic Transmission from the Preoptic Area , 2002, The Journal of Neuroscience.

[15]  A. Iggo,et al.  A quantitative study of sensitive cutaneous thermoreceptors with C afferent fibres , 1960, The Journal of physiology.

[16]  O. Ottersen,et al.  Cervicothalamic tract terminals are enriched in glutamate-like immunoreactivity: an electron microscopic double-labeling study in the cat , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  S. Nakai,et al.  Neuronal circuitries involved in thermoregulation , 2000, Autonomic Neuroscience.

[18]  N. L. Chamberlin,et al.  Topographic organization of cardiovascular responses to electrical and glutamate microstimulation of the parabrachial nucleus in the rat , 1992, The Journal of comparative neurology.

[19]  C. Saper,et al.  Spinal and trigeminal dorsal horn projections to the parabrachial nucleus in the rat , 1985, The Journal of comparative neurology.

[20]  D. McKemy,et al.  Lessons from peppers and peppermint: the molecular logic of thermosensation , 2003, Current Opinion in Neurobiology.

[21]  N. Null Minimum Design Loads for Buildings and Other Structures , 2003 .

[22]  T. Bartsch,et al.  Rhythmicity in single fiber postganglionic activity supplying the rat tail. , 1999, Journal of neurophysiology.

[23]  A. Craig,et al.  Spinothalamic lamina I neurones selectively responsive to cutaneous warming in cats , 2001, The Journal of physiology.

[24]  S. Morrison,et al.  Central control of thermogenesis in mammals , 2008, Experimental physiology.

[25]  J. Besson,et al.  Organization of efferent projections from the parabrachial area to the hypothalamus: a Phaseolus vulgaris‐leucoagglutinin study in the rat , 1997, The Journal of comparative neurology.

[26]  Clifford B. Saper,et al.  Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat , 1984, Brain Research Reviews.

[27]  M. McKinley,et al.  Roles of two preoptic cell groups in tonic and febrile control of rat tail sympathetic fibers. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[28]  R. McAllen,et al.  Functional topography of the dorsomedial hypothalamus , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[29]  C. Saper,et al.  Efferent connections of the parabrachial nucleus in the rat , 1980, Brain Research.

[30]  Y. Zotterman,et al.  The specificity of afferent cutaneous C fibres in mammals. , 1960, Acta physiologica Scandinavica.

[31]  H. T. Hammel,et al.  Regulation of internal body temperature. , 1968, Annual review of physiology.

[32]  J. Boulant,et al.  The effect of skin temperature on the hypothalamic control of heat loss and heat production , 1977, Brain Research.

[33]  C. E. Huckaba,et al.  A feedback-feedforward mechanism describing the interaction of central and peripheral signals in human thermoregulation , 1971, International journal of biometeorology.

[34]  S. Morrison,et al.  A thermosensory pathway that controls body temperature , 2008, Nature Neuroscience.

[35]  A. A. Romanovsky,et al.  CALL FOR PAPERS Physiology and Pharmacology of Temperature Regulation Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system , 2007 .

[36]  J M Besson,et al.  Spino (trigemino) parabrachiohypothalamic pathway: electrophysiological evidence for an involvement in pain processes. , 1995, Journal of neurophysiology.

[37]  S. Morrison,et al.  Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.