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Central control of body temperature

Shaun F. Morrison

F1000Research · 2016 · Review

doi:10.12688/f1000research.7958.1

Abstract

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 23, 2026. Paragraph numbers are ours, so an answer can point at one.

Body temperature (T core) is a critical homeostatic parameter influencing cellular function and organismal survival. Life-threatening protein denaturation looms as T core increases, and reductions in membrane fluidity, ion fluxes, and enzyme performance accompany significant reductions in T core. The fundamental central neural circuits for thermoregulation orchestrate behavioral and autonomic repertoires that maintain T core during thermal challenges, sensed by thermal receptors, that arise from either the ambient or the internal (e.g., during exercise) environment. A variety of other neural circuits and neurochemical modulators impinge on the fundamental thermoregulatory pathways to produce the alterations in T core that occur with circadian and ultradian periodicities, and those that accompany many behavioral states, such as fever during sickness, increased T core during psychological stress and at ovulation, and reductions in T core during sleep, sepsis, or exposure to metabolic distress (e.g., hypoxia and starvation). Recent research in the central nervous system (CNS) control of T core focuses principally on: (a) elaborating the CNS pathways and neurotransmitter systems involved in the fundamental central thermoregulatory network; (b) the modulation of activity within the fundamental central thermoregulatory network by non-thermal factors and behavioral states; and (c) pharmacological manipulation of the CNS thermoregulatory network for a variety of therapeutic goals (e.g., reducing T core to produce therapeutic hypothermia in stroke victims).

In its simplest form, the fundamental thermoregulatory network can be modeled as a reflex, in which a central integrative circuit alters the activity of thermoeffector mechanisms in response to an input from the combination of peripheral (i.e., skin) and central (i.e., visceral and brain) thermoreceptors that provides a consolidated assessment of T core and, importantly, of imminent threats to T core. The primary thermoeffector mechanisms recruited for both cold defense and centrally driven hyperthermias (e.g., fever) include: (a) thermoregulatory behaviors to reduce the loss of heat produced during basal metabolism; (b) cutaneous vasoconstriction (CVC) to conserve heat in the body core and limit heat loss to the environment; and (c) heat production (thermogenesis). The principal sources of metabolic heat production, beyond those contributing to basal metabolic rate (e.g., pumping ions across membranes), are brown adipose tissue (BAT), whose sympathetic neural input fuels mitochondria that shunt proton fluxes into heat production, and shivering behavior in skeletal muscle, dependent on the inefficiency of ATP utilization to generate heat. Effector mechanisms for heat defense include: (a) thermoregulatory behavior to increase heat loss; (b) cutaneous vasodilation, which in humans includes a sympathetic vasodilator outflow,, combined with increased cardiac output and visceral vasoconstriction – to facilitate core heat loss from the body surface; and (c) evaporative cooling (e.g., sweating).

Apart from important “first responders”, the CNS pathways controlling and mediating thermoregulatory behaviors remain incompletely defined –. Along these same lines, most research subjects are furry mammals that are strongly dependent on non-sweating mechanisms for evaporative cooling. Although this has limited the available detail on the CNS pathways regulating human sweating,,, considerable insight has been gained on the CNS regulation of other mechanisms of evaporative cooling, such as panting –. Additionally, since most of the basic neuroscience of CNS thermoregulatory pathways has been derived from experiments in rodents, including the exclusively in vitro studies of neurons with intrinsic thermosensitivity, the translation of the conclusions, including the circuit model in Figure 1, to humans must be cautiously undertaken (e.g., ). Finally, although considerable progress has been achieved in the relatively young field of the neuroscience of thermoregulation, the synthesis ( Figure 1) of our understanding of this multifaceted neural network controlling multiple thermoeffectors represents a working model, with the expectation of revisions and added detail.

The CNS thermoregulatory control of the sympathetic outflows mediating CVC and BAT thermogenesis and of the somatic motoneurons producing shivering is effected through parallel but distinct, effector-specific, integrative/efferent circuits ( Figure 1, and reviewed in – ) that share common peripheral thermal sensory inputs. The hypothalamus contains the primary integrative and rostral efferent components of these circuits. Although many details of the preoptic area (POA) microcircuitry for thermoregulation remain to be elucidated, neurons in the POA are postulated to integrate ascending peripheral thermosensory signals with local thermosensitivity to regulate the output of BAT and shivering thermogenesis-promoting neurons in the dorsomedial hypothalamus (DMH), and of CVC-promoting neurons in the median preoptic nucleus (MnPO),.

The POA regulation of DMH thermogenesis-promoting neurons represents the balance between a GABAergic inhibition, and a glutamatergic excitation; the latter inputs, potentially arising from neurons in the MnPO that project to the DMH, are synaptically connected to BAT and express the leptin receptor. These glutamatergic inputs to DMH could provide the excitation required to drive the BAT sympathoexcitatory neurons and the shivering-promoting neurons in DMH when their POA inhibitory input is reduced during skin cooling or fever. Although intrinsically warm-sensitive (W-S) ( Figure 1), POA neurons –, generally located in the medial preoptic area (MPA), are postulated to play a key role in central thermoregulation by providing a prominent core temperature-modulated, GABAergic regulation of thermogenesis-promoting neurons in DMH ( Figure 1), the considerable direct functional evidence required to establish this attractive hypothesis has yet to be obtained. Different thermal sensitivities or neurochemical modulation among populations of temperature-sensitive POA neurons may underlie the differential responsiveness of different effectors to changes in cutaneous versus brain temperatures as well as the significant alterations in thermoeffector activation during different sleep phases. Through their responses to immune signaling molecules, neurons in the POA are also the primary site for the organization and maintenance of the febrile response to inflammation and infection, which includes the stimulation of CVC, and shivering (“chills”) and BAT thermogenesis mediated by the action of prostaglandin E 2 (PGE 2) on its EP3 receptors –. Similarly, the fundamental thermoregulatory network mediates stress-induced hyperthermia –. Unraveling the complexity of the thermoregulatory circuitry in the hypothalamus,,, –, including the phenotypic characterization of the projection neurons and their synaptic interactions that mediate the circadian and many behavioral, modulations in T core, continues to pose significant research challenges for understanding the “heart” of the CNS thermoregulatory network. The downstream targets of the hypothalamic projection neurons for thermoregulation are the sympathetic and somatic premotor neurons in the rostral ventromedial medulla, centered on the rostral raphe pallidus (rRPa). Midbrain (e.g., periaqueductal gray – and retrorubral field ) and medullary (e.g., ventrolateral medulla and nucleus of the solitary tract (NTS), ) pathways to these premotor neurons exert important modulatory influences on the thermoregulatory activation of thermoeffector organs (reviewed in, ). These premotor neurons, in turn, excite CVC and BAT sympathetic preganglionic neurons and α-motoneurons and γ-motoneurons, in the spinal cord.

Cold and warm thermoreceptors in the skin and viscera provide the extracranial thermal signals relating to skin temperature and T core. These are integrated with the brain temperature information potentially derived from the discharge of W-S, GABAergic preoptic neurons of the central thermoregulatory network to regulate thermoeffector activities. The membranes of thermoreceptor afferent neurons contain transient receptor potential (TRP) cation channels whose temperature-dependent conductances transduce skin temperature into primary thermoreceptor afferent neuronal activity. The TRPM8 channel, activated by menthol and cooling, is the strongest candidate for the cutaneous cold receptor (reviewed in ). The identity of the peripheral warm receptor remains to be established, but the warm-sensing mechanism of preoptic neurons, though still debated –, is unlikely to involve a transient receptor potential (TRP) channel. Primary thermoreceptor dorsal root ganglion neurons synapse on thermoreceptive-specific, lamina I spinal (or trigeminal) dorsal horn cells, and these, in turn, collateralize to innervate the thalamus, providing the neural substrate for cutaneous thermosensory perception and localization,, and the pontine lateral parabrachial nucleus (LPB),, which is responsible for triggering involuntary (e.g., autonomic and shivering) thermoregulatory responses. Spinal lamina I skin cooling-responsive neurons provide a glutamatergic excitation to neurons in the external lateral subdivision of the lateral parabrachial nucleus (LPBel), which, in turn, project principally to the MnPO of the POA,, while a parallel, spinoparabrachial glutamatergic pathway excites POA-projecting neurons in the dorsal subnucleus of the LPB (LPBd), in response to skin warming. Thus, activations of POA-projecting LPBd and LPBel neurons, driven respectively by cutaneous, and likely visceral, warm and cold thermoreceptor stimuli, initiate heat defense and cold defense inhibitions and excitations, respectively, in CVC sympathetic outflow and cutaneous blood flow, in BAT sympathetic outflow and BAT thermogenesis, and in shivering EMGs and shivering thermogenesis to maintain a homeostatic T core.

Synaptic integration sites throughout the core thermoregulatory network provide the substrate for a wide variety of non-thermal physiological parameters, disease processes, neuromodulators, and drugs to influence the central regulation of T core (reviewed in ). For example, the high metabolic rate of BAT and shivering skeletal muscles during thermogenesis cannot be sustained without a dependable supply of metabolic fuels, particularly oxygen, lipolytic by-products, and glucose. Thus, the CNS networks driving cold-defensive and behavioral BAT activation or shivering are strongly inhibited by signals reflecting a reduction in the short- and long-term availability of these fuel molecules essential for BAT and skeletal muscle metabolism. Similarly, as hypovolemia progresses during dehydration, the ensuing hyperosmolarity reduces the thermoregulatory drive for sweating,,, which serves to prevent cardiovascular collapse. Some viscerosensory afferents with axons in the vagus nerve and synapsing on second-order neurons in the NTS can also influence BAT activity, and shivering responses and thus are expected to influence the regulation of T core. For instance, vagal afferents convey the “metabolic” signals that produce the inhibition of BAT activity induced by upregulation of hepatic glucokinase and the BAT activation following either intragastric delivery of the TRP agonist, capsiate, or the presence of lipids in the duodenum. Another influence on T core includes a prominent hypothermia during motion sickness and nausea, for which the pathways relating vestibular stimulation to inhibition of CVC and thermogenesis remain to be elaborated.

Providing an additional layer of complexity in the CNS regulation of T core is the presence of the thermally responsive TRPV1 channel in the membranes of a variety of classically non-thermal, unmyelinated afferents – that may have access to central thermoregulatory circuits, including via NTS neurons that can inhibit thermogenesis. The finding that the TRPV1 responsiveness to local brain temperature alters spontaneous glutamate release from the terminals of unmyelinated vagal afferents, provides a potential substrate for T core to modulate the activity of second-order sensory neurons in NTS that modulate thermoeffector activation. Importantly, TRPV1 channels are also activated by non-thermal factors, including low (or high) pH, inorganic cations, or endovanilloids, thereby providing a basis for such factors to influence thermoeffector activation and thus T core. For instance, TRPV1 channels, potentially on the terminals of afferents in the peritoneum, are stimulated by an endogenous ligand to tonically inhibit BAT thermogenesis, which results in a hyperthermic response to TRPV1 antagonist administration,. Although these afferents were not directly tested for their thermal responsiveness, the hyperthermic response to TRPV1 antagonism was not altered by changes in T core. The relative influences and the interactions of thermal and non-thermal stimuli on the conductance of the relevant TRPV1 channels could play a role in determining their effect on the level of thermoeffector activation to thermoreceptor stimuli.

Interest in pharmacological modulation of the central thermoregulatory network has focused: (a) on reducing CVC and thermogenesis to lower T core; and (b) on augmenting thermogenesis to elevate energy expenditure with the goal of weight loss through consumption of the high-energy lipid stores in white adipose tissue. Novel approaches to reducing T core would have immediate benefits in treating intractable fevers that are unresponsive to cyclooxygenase inhibitors. Therapeutic hypothermia can have beneficial effects on survival and on reducing brain and tissue damage in ischemic insults such as cardiac arrest, stroke, and neonatal encephalopathy –. Extended space travel (e.g., Mars One) also may require pharmacological induction of a hypothermic, hibernation-like state to reduce energy consumption and psychological stress.

Under basal metabolic and movement conditions, changes in T core must arise from changes in the level of activation of thermoeffector tissues. Although modulating neuronal discharge at any site within the central thermoregulatory network would be expected to alter T core, centrally generated hyperthermias, such as fever, that arise from altered activity in hypothalamic thermoregulatory neurons could be most effectively reduced by manipulating thermoeffector efferent pathways,. Indeed, directly inhibiting the discharge of neurons in the rRPa area, including the functionally significant premotor neurons that control the principal thermoeffectors, produced a fall in brain temperature of approximately 14°C in an ambient environment of 15°C, and stimulation of α2 adrenergic receptors in the rRPa could completely block or prevent a lipopolysaccharide-evoked fever. Similarly, central administration of an adenosine A1 receptor (A1AR) agonist reduced rat T core by 10°C in an ambient temperature of 15°C and mouse T core by 5°C in an ambient temperature of 4°C. Of particular interest, in rats, this hypothermia, which was produced by a blockade of the cold-evoked activation of BAT and shivering thermogenesis, was long-lasting and paralleled by marked reductions in heart and respiratory rate, in EEG, and in behavior —all reminiscent of those occurring in hibernation and torpor, which require central stimulation of the A1AR –. The discovery of a role for TRP channels in thermal sensation and in thermoeffector activation has stimulated research into the pharmacological modulation of TRP channels in the central thermoregulatory network to abrogate the normal cold defense mechanisms and allow T core to fall in a cool ambient environment. By reducing the activation of cooling-responsive skin thermoreceptors, a TRPM8 antagonist reduced rat T core by approximately 1°C when the rats were in an ambient temperature of 19°C. Stimulating TRPV1 reduced mouse T core by approximately 12°C when mice were exposed to a 10°C ambient temperature, and this effect was potentiated by the addition of a TRPM8 antagonist. The location of the relevant, hypothermic TRPV1 channels remains unknown.

Not only is BAT a thermogenic thermoeffector, including in adult humans –, but through its consumption of lipid and glucose energy stores and oxygen, thermogenic metabolism in BAT is a neurally regulated contributor to energy homeostasis. Thus, particularly in the face of an elevated consumption of energy-rich food (e.g., a high-fat diet), a chronic reduction in cooling-evoked BAT thermogenesis would contribute to the augmented adipose energy stores that characterize obesity. Indeed, mice without BAT exhibit a propensity for obesity and diabetes,; conversely, overexpression of uncoupling protein-1 (UCP-1), principally responsible for thermogenesis in BAT, mitigates obesity induced by a high-fat diet. Several anti-obesity therapies currently being explored are based on increased activation of BAT thermogenesis, through either activation of the central thermoregulatory network to increase the sympathetic outflow to BAT or an alteration in the cellular biochemical pathways in brown adipocytes or a hyperplasia of BAT to augment thermogenesis. The consistent findings that obese humans have significantly reduced cooling-activated BAT –,, and that the basal (i.e., principally cooling-evoked) sympathetic activation of BAT is reduced in rats fed a high-fat diet,, and that a vagal afferent input to the NTS mediates the reduced cooling-evoked BAT activity in rats fed a high-fat diet not only support a role for reduced BAT activity in the excess adipose accumulation of obesity but also highlight the significance of non-thermal inputs to the central thermoregulatory network,, in influencing even the most basic thermoregulatory responses.

Considerable progress has been achieved in revealing the functional organization of the dedicated thermoregulatory network within the CNS that provides the fundamental neural control of the thermoregulatory effectors: thermoregulatory behavior, CVC, and BAT and shivering thermogenesis, although many of the details of the neurophysiology and neuroanatomy of the central thermoregulatory network remain active areas of investigation. The changes in T core that accompany a wide range of behaviors and in response to many hormones and drugs arise through altered non-thermal inputs to, or neurochemical modulation of, the neural activity within the fundamental thermoregulatory network. The latter, as well as thermoreceptor-based strategies, are being researched as therapeutic approaches in which the central thermoregulatory networks are recruited to alter T core and metabolism.

References 115

  1. 1.

    Ootsuka Y de Menezes RC Zaretsky DV: Brown adipose tissue thermogenesis heats brain and body as part of the brain-coordinated ultradian basic rest-activity cycle. Neuroscience. 2009;164(2):849–61.

    Not in our library10.1016/j.neuroscience.2009.08.013

  2. 2.

    Vujovic N Gooley JJ Jhou TC: Projections from the subparaventricular zone define four channels of output from the circadian timing system. J Comp Neurol. 2015;523(18):2714–37.

    Not in our library10.1002/cne.23812

  3. 3.

    Romanovsky AA: Do fever and anapyrexia exist? Analysis of set point-based definitions. Am J Physiol Regul Integr Comp Physiol. 2004;287(4):R992–5.

    Not in our library10.1152/ajpregu.00068.2004

  4. 4.

    Werner J: System properties, feedback control and effector coordination of human temperature regulation. Eur J Appl Physiol. 2010;109(1):13–25.

    Not in our library10.1007/s00421-009-1216-1

  5. 5.

    Wallin BG Charkoudian N: Sympathetic neural control of integrated cardiovascular function: insights from measurement of human sympathetic nerve activity. Muscle Nerve. 2007;36(5):595–614.

    Not in our library10.1002/mus.20831

  6. 6.

    Smith CJ Johnson JM: Responses to hyperthermia. Optimizing heat dissipation by convection and evaporation: Neural control of skin blood flow and sweating in humans. Auton Neurosci. 2016;196:25–36.

    Not in our library10.1016/j.autneu.2016.01.002

  7. 7.

    Crandall CG: Heat stress and baroreflex regulation of blood pressure. Med Sci Sports Exerc. 2008;40(12):2063–70.

    Not in our library10.1249/mss.0b013e318180bc98

  8. 8.

    Escourrou P Freund PR Rowell LB: Splanchnic vasoconstriction in heat-stressed men: role of renin-angiotensin system. J Appl Physiol Respir Environ Exerc Physiol. 1982;52(6):1438–43.

    Not in our library10.1152/jappl.1982.52.6.1438

  9. 9.

    Kregel KC Wall PT Gisolfi CV: Peripheral vascular responses to hyperthermia in the rat. J Appl Physiol (1985). 1988;64(6):2582–8.

    Not in our library10.1152/jappl.1988.64.6.2582

  10. 10.

    Minson CT Wladkowski SL Pawelczyk JA: Age, splanchnic vasoconstriction, and heat stress during tilting. Am J Physiol. 1999;276(1 Pt 2):R203–12.

    Not in our library10.1152/ajpregu.1999.276.1.r203

  11. 11.

    Satinoff E Rutstein J: Behavioral thermoregulation in rats with anterior hypothalamic lesions. J Comp Physiol Psychol. 1970;71(1):77–82.

    Not in our library10.1037/h0028959

  12. 12.

    Nagashima K Nakai S Tanaka M: Neuronal circuitries involved in thermoregulation. Auton Neurosci. 2000;85(1–3):18–25.

    Not in our library10.1016/s1566-0702(00)00216-2

  13. 13.

    Almeida MC Steiner AA Branco LG: Cold-seeking behavior as a thermoregulatory strategy in systemic inflammation. Eur J Neurosci. 2006;23(12):3359–67.

    Not in our library10.1111/j.1460-9568.2006.04854.x

  14. 14.
    Neural substrate of cold-seeking behavior in endotoxin shock. · 2006
    Not checked
  15. 15.

    Terrien J Perret M Aujard F: Behavioral thermoregulation in mammals: a review. Front Biosci (Landmark Ed). 2011;16:1428–44.

    Not in our library10.2741/3797

  16. 16.

    Shibasaki M Crandall CG: Mechanisms and controllers of eccrine sweating in humans. Front Biosci (Schol Ed). 2010;2:685–96.

    Not in our library10.2741/s94

  17. 17.

    Farrell MJ Trevaks D Taylor NA: Regional brain responses associated with thermogenic and psychogenic sweating events in humans. J Neurophysiol. 2015;114(5):2578–87.

    Not in our library10.1152/jn.00601.2015

  18. 18.

    McKinley MJ McAllen RM Whyte D: Central osmoregulatory influences on thermoregulation. Clin Exp Pharmacol Physiol. 2008;35(5–6):701–5.

    Not in our library10.1111/j.1440-1681.2007.04833.x

  19. 19.

    Poon CS: Optimal interaction of respiratory and thermal regulation at rest and during exercise: role of a serotonin-gated spinoparabrachial thermoafferent pathway. Respir Physiol Neurobiol. 2009;169(3):234–42.

    Not in our library10.1016/j.resp.2009.09.006

  20. 20.

    McKinley MJ Yao ST Uschakov A: The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis. Acta Physiol (Oxf). 2015;214(1):8–32.

    Not in our library10.1111/apha.12487

  21. 21.

    McAllen RM Farrell M Johnson JM: Human medullary responses to cooling and rewarming the skin: a functional MRI study. Proc Natl Acad Sci U S A. 2006;103(3):809–13.

    Not in our library10.1073/pnas.0509862103

  22. 22.

    Morrison SF Nakamura K: Central neural pathways for thermoregulation. Front Biosci (Landmark Ed). 2011;16:74–104.

    Not in our library10.2741/3677

  23. 23.

    Nakamura K: Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol. 2011;301(5):R1207–28.

    Not in our library10.1152/ajpregu.00109.2011

  24. 24.

    Morrison SF Madden CJ: Central nervous system regulation of brown adipose tissue. Compr Physiol. 2014;4(4):1677–713.

    Not in our library10.1002/cphy.c140013

  25. 25.

    Morrison SF Madden CJ Tupone D: Central neural regulation of brown adipose tissue thermogenesis and energy expenditure. Cell Metab. 2014;19(5):741–56.

    Not in our library10.1016/j.cmet.2014.02.007

  26. 26.

    Nakamura K Morrison SF: Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R127–36.

    Not in our library10.1152/ajpregu.00427.2006

  27. 27.

    Nakamura K Morrison SF: Central efferent pathways for cold-defensive and febrile shivering. J Physiol. 2011;589(Pt 14):3641–58.

    Not in our library10.1113/jphysiol.2011.210047

  28. 28.

    Tanaka M McKinley MJ McAllen RM: Preoptic-raphé connections for thermoregulatory vasomotor control. J Neurosci. 2011;31(13):5078–88.

    Not in our library10.1523/jneurosci.6433-10.2011

  29. 29.

    Tanaka M McKinley MJ McAllen RM: Role of an excitatory preoptic-raphé pathway in febrile vasoconstriction of the rat's tail. Am J Physiol Regul Integr Comp Physiol. 2013;305(12):R1479–89.

    Not in our library10.1152/ajpregu.00401.2013

  30. 30.

    Cao WH Fan W Morrison SF: Medullary pathways mediating specific sympathetic responses to activation of dorsomedial hypothalamus. Neuroscience. 2004;126(1):229–40.

    Not in our library10.1016/j.neuroscience.2004.03.013

  31. 31.

    Nakamura Y Nakamura K Matsumura K: Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus. Eur J Neurosci. 2005;22(12):3137–46.

    Not in our library10.1111/j.1460-9568.2005.04515.x

  32. 32.

    Madden CJ 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. 2004;286(2):R320–5.

    Not in our library10.1152/ajpregu.00515.2003

  33. 33.

    Dimitrov EL Kim YY Usdin TB: Regulation of hypothalamic signaling by tuberoinfundibular peptide of 39 residues is critical for the response to cold: a novel peptidergic mechanism of thermoregulation. J Neurosci. 2011;31(49):18166–79.

    Not in our library10.1523/jneurosci.2619-11.2011

  34. 34.

    Zhang Y Kerman IA Laque A: Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits. J Neurosci. 2011;31(5):1873–84.

    Not in our library10.1523/jneurosci.3223-10.2011

  35. 35.

    Zhang YH Yanase-Fujiwara M Hosono T: Warm and cold signals from the preoptic area: which contribute more to the control of shivering in rats? J Physiol. 1995;485(Pt 1):195–202.

    Not in our library10.1113/jphysiol.1995.sp020723

  36. 36.

    Boulant JA Dean JB: Temperature receptors in the central nervous system. Annu Rev Physiol. 1986;48:639–54.

    Not in our library10.1146/annurev.ph.48.030186.003231

  37. 37.

    Griffin JD Kaple ML Chow AR: Cellular mechanisms for neuronal thermosensitivity in the rat hypothalamus. J Physiol. 1996;492(Pt 1):231–42.

    Not in our library10.1113/jphysiol.1996.sp021304

  38. 38.

    Lundius EG Sanchez-Alavez M Ghochani Y: Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons. J Neurosci. 2010;30(12):4369–81.

    Not in our library10.1523/jneurosci.0378-10.2010

  39. 39.

    Griffin JD Saper CB Boulant JA: Synaptic and morphological characteristics of temperature-sensitive and -insensitive rat hypothalamic neurones. J Physiol. 2001;537(Pt 2):521–35.

    Not in our library10.1111/j.1469-7793.2001.00521.x

  40. 40.

    Ootsuka Y McAllen RM: Comparison between two rat sympathetic pathways activated in cold defense. Am J Physiol Regul Integr Comp Physiol. 2006;291(3):R589–95.

    Not in our library10.1152/ajpregu.00850.2005

  41. 41.

    Glotzbach SF Heller HC: Central nervous regulation of body temperature during sleep. Science. 1976;194(4264):537–9.

    Not in our library10.1126/science.973138

  42. 42.

    Scammell TE Elmquist JK Griffin JD: Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways. J Neurosci. 1996;16(19):6246–54.

    Not in our library10.1523/jneurosci.16-19-06246.1996

  43. 43.

    Nakamura K Kaneko T Yamashita Y: Immunohistochemical localization of prostaglandin EP3 receptor in the rat nervous system. J Comp Neurol. 2000;421(4):543–69.

    Not in our library10.1002/(sici)1096-9861(20000612)421:4<543::aid-cne6>3.0.co;2-3

  44. 44.

    Nakamura K Matsumura K Kaneko T: The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area. J Neurosci. 2002;22(11):4600–10.

    Not in our library10.1523/jneurosci.22-11-04600.2002

  45. 45.

    Lazarus M Yoshida K Coppari R: EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses. Nat Neurosci. 2007;10(9):1131–3.

    Not in our library10.1038/nn1949

  46. 46.

    Lkhagvasuren B Nakamura Y Oka T: Social defeat stress induces hyperthermia through activation of thermoregulatory sympathetic premotor neurons in the medullary raphe region. Eur J Neurosci. 2011;34(9):1442–52.

    Not in our library10.1111/j.1460-9568.2011.07863.x

  47. 47.

    Kataoka N Hioki H Kaneko T: Psychological stress activates a dorsomedial hypothalamus-medullary raphe circuit driving brown adipose tissue thermogenesis and hyperthermia. Cell Metab. 2014;20(2):346–58.

    Not in our library10.1016/j.cmet.2014.05.018

  48. 48.

    Mohammed M Ootsuka Y Blessing W: Brown adipose tissue thermogenesis contributes to emotional hyperthermia in a resident rat suddenly confronted with an intruder rat. Am J Physiol Regul Integr Comp Physiol. 2014;306(6):R394–400.

    Not in our library10.1152/ajpregu.00475.2013

  49. 49.

    Nakamura K Morrison SF: Preoptic mechanism for cold-defensive responses to skin cooling. J Physiol. 2008;586(10):2611–20.

    Not in our library10.1113/jphysiol.2008.152686

  50. 50.

    Tanaka M McKinley MJ McAllen RM: Roles of two preoptic cell groups in tonic and febrile control of rat tail sympathetic fibers. Am J Physiol Regul Integr Comp Physiol. 2009;296(4):R1248–57.

    Not in our library10.1152/ajpregu.91010.2008

  51. 51.

    Yoshida K Li X Cano G: Parallel preoptic pathways for thermoregulation. J Neurosci. 2009;29(38):11954–64.

    Not in our library10.1523/jneurosci.2643-09.2009

  52. 52.

    Osaka T: Thermoregulatory responses elicited by microinjection of L-glutamate and its interaction with thermogenic effects of GABA and prostaglandin E 2 in the preoptic area. Neuroscience. 2012;226:156–64.

    Not in our library10.1016/j.neuroscience.2012.08.048

  53. 53.

    Mohammed M Kulasekara K De Menezes RC: Inactivation of neuronal function in the amygdaloid region reduces tail artery blood flow alerting responses in conscious rats. Neuroscience. 2013;228:13–22.

    Not in our library10.1016/j.neuroscience.2012.10.008

  54. 54.

    Ootsuka Y Mohammed M: Activation of the habenula complex evokes autonomic physiological responses similar to those associated with emotional stress. Physiol Rep. 2015;3(2): pii: e12297.

    Not in our library10.14814/phy2.12297

  55. 55.

    Zhang YH Hosono T Yanase-Fujiwara M: Effect of midbrain stimulations on thermoregulatory vasomotor responses in rats. J Physiol. 1997;503(Pt 1):177–86.

    Not in our library10.1111/j.1469-7793.1997.177bi.x

  56. 56.

    Yoshida K Maruyama M Hosono T: Fos expression induced by warming the preoptic area in rats. Brain Res. 2002;933(2):109–17.

    Not in our library10.1016/s0006-8993(02)02287-4

  57. 57.

    Yoshida K Konishi M Nagashima K: Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter. Neuroscience. 2005;133(4):1039–46.

    Not in our library10.1016/j.neuroscience.2005.03.044

  58. 58.

    Shibata M Uno T Hashimoto M: Disinhibition of lower midbrain neurons enhances non-shivering thermogenesis in anesthetized rats. Brain Res. 1999;833(2):242–50.

    Not in our library10.1016/s0006-8993(99)01532-2

  59. 59.

    Cao WH Madden CJ Morrison SF: Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius. Am J Physiol Regul Integr Comp Physiol. 2010;299(1):R277–90.

    Not in our library10.1152/ajpregu.00039.2010

  60. 60.

    Tupone D Madden CJ Morrison SF: Central activation of the A1 adenosine receptor (A1AR) induces a hypothermic, torpor-like state in the rat. J Neurosci. 2013;33(36):14512–25.

    Not in our library10.1523/jneurosci.1980-13.2013

  61. 61.

    Sato H Hashitani T Isobe Y: Descending influences from nucleus raphe magnus on fusimotor neurone activity in rats. J Therm Biol. 1990;15(3–4):259–65.

    Not in our library10.1016/0306-4565(90)90012-7

  62. 62.

    Tanaka M Owens NC Nagashima K: Reflex activation of rat fusimotor neurons by body surface cooling, and its dependence on the medullary raphe. J Physiol. 2006;572(Pt 2):569–83.

    Not in our library10.1113/jphysiol.2005.102400

  63. 63.

    Almeida MC Hew-Butler T Soriano RN: Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. J Neurosci. 2012;32(6):2086–99.

    Not in our library10.1523/jneurosci.5606-11.2012

  64. 64.

    Tabarean IV Behrens MM Bartfai T: Prostaglandin E 2-increased thermosensitivity of anterior hypothalamic neurons is associated with depressed inhibition. Proc Natl Acad Sci U S A. 2004;101(8):2590–5.

    Not in our library10.1073/pnas.0308718101

  65. 65.

    Boulant JA: Counterpoint: Heat-induced membrane depolarization of hypothalamic neurons: an unlikely mechanism of central thermosensitivity. Am J Physiol Regul Integr Comp Physiol. 2006;290(5):R1481–4; discussion R1484.

    Not in our library10.1152/ajpregu.00655.2005

  66. 66.

    Kobayashi S Hori A Matsumura K: Point: Heat-induced membrane depolarization of hypothalamic neurons: a putative mechanism of central thermosensitivity. Am J Physiol Regul Integr Comp Physiol. 2006;290(5):R1479–80; discussion R1484.

    Not in our library10.1152/ajpregu.00655.2005

  67. 67.

    Wechselberger M Wright CL Bishop GA: Ionic channels and conductance-based models for hypothalamic neuronal thermosensitivity. Am J Physiol Regul Integr Comp Physiol. 2006;291(3):R518–29.

    Not in our library10.1152/ajpregu.00039.2006

  68. 68.

    Craig AD: How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci. 2002;3(8):655–66.

    Not in our library10.1038/nrn894

  69. 69.

    Craig AD Bushnell MC Zhang ET: A thalamic nucleus specific for pain and temperature sensation. Nature. 1994;372(6508):770–3.

    Not in our library10.1038/372770a0

  70. 70.

    Hylden JL Anton F Nahin RL: Spinal lamina I projection neurons in the rat: collateral innervation of parabrachial area and thalamus. Neuroscience. 1989;28(1):27–37.

    Not in our library10.1016/0306-4522(89)90229-7

  71. 71.

    Li J Xiong K Pang Y: Medullary dorsal horn neurons providing axons to both the parabrachial nucleus and thalamus. J Comp Neurol. 2006;498(4):539–51.

    Not in our library10.1002/cne.21068

  72. 72.

    Bratincsák A Palkovits M: Activation of brain areas in rat following warm and cold ambient exposure. Neuroscience. 2004;127(2):385–97.

    Not in our library10.1016/j.neuroscience.2004.05.016

  73. 73.

    Nakamura K Morrison SF: A thermosensory pathway that controls body temperature. Nat Neurosci. 2008;11(1):62–71.

    Not in our library10.1038/nn2027

  74. 74.

    Nakamura K Morrison SF: A thermosensory pathway mediating heat-defense responses. Proc Natl Acad Sci U S A. 2010;107(19):8848–53.

    Not in our library10.1073/pnas.0913358107

  75. 75.

    Madden CJ Morrison SF: Hypoxic activation of arterial chemoreceptors inhibits sympathetic outflow to brown adipose tissue in rats. J Physiol. 2005;566(Pt 2):559–73.

    Not in our library10.1113/jphysiol.2005.086322

  76. 76.

    Madden CJ: Glucoprivation in the ventrolateral medulla decreases brown adipose tissue sympathetic nerve activity by decreasing the activity of neurons in raphe pallidus. Am J Physiol Regul Integr Comp Physiol. 2012;302(2):R224–32.

    Not in our library10.1152/ajpregu.00449.2011

  77. 77.

    Baker MA Doris PA: Control of evaporative heat loss during changes in plasma osmolality in the cat. J Physiol. 1982;328(1):535–45.

    Not in our library10.1113/jphysiol.1982.sp014282

  78. 78.

    Takamata A Mack GW Gillen CM: Osmoregulatory modulation of thermal sweating in humans: reflex effects of drinking. Am J Physiol. 1995;268(2 Pt 2):R414–22.

    Not in our library10.1152/ajpregu.1995.268.2.r414

  79. 79.

    Kenney WL Stanhewicz AE Bruning RS: Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation? Eur J Appl Physiol. 2014;114(3):467–79.

    Not in our library10.1007/s00421-013-2652-5

  80. 80.

    Székely M: The vagus nerve in thermoregulation and energy metabolism. Auton Neurosci. 2000;85(1–3):26–38.

    Not in our library10.1016/s1566-0702(00)00217-4

  81. 81.

    Tsukita S Yamada T Uno K: Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab. 2012;16(6):825–32.

    Not in our library10.1016/j.cmet.2012.11.006

  82. 82.

    Ono K Tsukamoto-Yasui M Hara-Kimura Y: Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses. J Appl Physiol (1985). 2011;110(3):789–98.

    Not in our library10.1152/japplphysiol.00128.2010

  83. 83.

    Blouet C Schwartz GJ: Duodenal lipid sensing activates vagal afferents to regulate non-shivering brown fat thermogenesis in rats. PLoS One. 2012;7(12):e51898.

    Not in our library10.1371/journal.pone.0051898

  84. 84.

    Ngampramuan S Cerri M Del Vecchio F: Thermoregulatory correlates of nausea in rats and musk shrews. Oncotarget. 2014;5(6):1565–75.

    Not in our library10.18632/oncotarget.1732

  85. 85.

    Romanovsky AA Almeida MC Garami A: The transient receptor potential vanilloid-1 channel in thermoregulation: a thermosensor it is not. Pharmacol Rev. 2009;61(3):228–61.

    Not in our library10.1124/pr.109.001263

  86. 86.

    Peters JH McDougall SJ Fawley JA: Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons. Neuron. 2010;65(5):657–69.

    Not in our library10.1016/j.neuron.2010.02.017

  87. 87.

    Fawley JA Hofmann ME Andresen MC: Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission. J Neurosci. 2014;34(24):8324–32.

    Not in our library10.1523/jneurosci.0315-14.2014

  88. 88.
    Temperature differentially facilitates spontaneous but not evoked glutamate release from cranial visceral primary afferents. · 2015
    Not checked
  89. 89.

    Shoudai K Peters JH McDougall SJ: Thermally active TRPV1 tonically drives central spontaneous glutamate release. J Neurosci. 2010;30(43):14470–5.

    Not in our library10.1523/jneurosci.2557-10.2010

  90. 90.

    Steiner AA Turek VF Almeida MC: Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J Neurosci. 2007;27(28):7459–68.

    Not in our library10.1523/jneurosci.1483-07.2007

  91. 91.

    Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.

    Not in our library10.1056/nejmoa012689

  92. 92.

    Shankaran S Laptook AR Ehrenkranz RA: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–84.

    Not in our library10.1056/nejmcps050929

  93. 93.

    van der Worp HB van Gijn J: Clinical practice. Acute ischemic stroke. N Engl J Med. 2007;357(6):572–9.

    Not in our library10.1056/nejmcp072057

  94. 94.

    Hemmen TM Lyden PD: Hypothermia after acute ischemic stroke. J Neurotrauma. 2009;26(3):387–91.

    Not in our library10.1089/neu.2008.0574

  95. 95.

    Madden CJ Tupone D Cano G: α2 Adrenergic receptor-mediated inhibition of thermogenesis. J Neurosci. 2013;33(5):2017–28.

    Not in our library10.1523/jneurosci.4701-12.2013

  96. 96.

    Tupone D Madden CJ Morrison SF: Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis. Front Neurosci. 2014;8:14.

    Not in our library10.3389/fnins.2014.00014

  97. 97.

    Cerri M Mastrotto M Tupone D: The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat. J Neurosci. 2013;33(7):2984–93.

    Not in our library10.1523/jneurosci.3596-12.2013

  98. 98.

    Muzzi M Blasi F Masi A: Neurological basis of AMP-dependent thermoregulation and its relevance to central and peripheral hyperthermia. J Cereb Blood Flow Metab. 2013;33(2):183–90.

    Not in our library10.1038/jcbfm.2012.157

  99. 99.

    Miyazawa S Shimizu Y Shiina T: Central A1-receptor activation associated with onset of torpor protects the heart against low temperature in the Syrian hamster. Am J Physiol Regul Integr Comp Physiol. 2008;295(3):R991–6.

    Not in our library10.1152/ajpregu.00142.2008

  100. 100.

    Jinka TR Tøien Ø, Drew KL: Season primes the brain in an arctic hibernator to facilitate entrance into torpor mediated by adenosine A 1 receptors. J Neurosci. 2011;31(30):10752–8.

    Not in our library10.1523/jneurosci.1240-11.2011

  101. 101.

    Iliff BW Swoap SJ: Central adenosine receptor signaling is necessary for daily torpor in mice. Am J Physiol Regul Integr Comp Physiol. 2012;303(5):R477–84.

    Not in our library10.1152/ajpregu.00081.2012

  102. 102.

    Feketa VV Balasubramanian A Flores CM: Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition. Am J Physiol Regul Integr Comp Physiol. 2013;305(9):R1040–50.

    Not in our library10.1152/ajpregu.00296.2013

  103. 103.

    Feketa VV Zhang Y Cao Z: Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. Crit Care Med. 2014;42(5):e355–63.

    Not in our library10.1097/ccm.0000000000000229

  104. 104.

    Cypess AM Lehman S Williams G: Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509–17.

    Not in our library10.1056/nejmoa0810780

  105. 105.

    Saito M Okamatsu-Ogura Y Matsushita M: High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58(7):1526–31.

    Not in our library10.2337/db09-0530

  106. 106.

    van Marken Lichtenbelt WD Vanhommerig JW Smulders NM: Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360(15):1500–8.

    Not in our library10.1056/nejmoa0808718

  107. 107.

    Orava J Nuutila P Lidell ME: Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011;14(2):272–9.

    Not in our library10.1016/j.cmet.2011.06.012

  108. 108.

    Lowell BB S-Susulic V Hamann A: Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993;366(6457):740–2.

    Not in our library10.1038/366740a0

  109. 109.

    Hamann A Flier JS Lowell BB: Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia. Endocrinology. 1996;137(1):21–9.

    Not in our library10.1210/endo.137.1.8536614

  110. 110.

    Kopecky J Clarke G Enerbäck S: Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest. 1995;96(6):2914–23.

    Not in our library10.1172/jci118363

  111. 111.

    Hanssen MJ van der Lans AA Brans B: Short-term cold acclimation recruits brown adipose tissue in obese humans. Diabetes. 2015; pii: db151372.

    Not in our library10.2337/db15-1372

  112. 112.

    Orava J Nuutila P Noponen T: Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans. Obesity (Silver Spring). 2013;21(11):2279–87.

    Not in our library10.1002/oby.20456

  113. 113.

    Sakaguchi T Arase K Fisler JS: Effect of a high-fat diet on firing rate of sympathetic nerves innervating brown adipose tissue in anesthetized rats. Physiol Behav. 1989;45(6):1177–82.

    Not in our library10.1016/0031-9384(89)90106-6

  114. 114.

    Levin BE: Reduced norepinephrine turnover in organs and brains of obesity-prone rats. Am J Physiol. 1995;268(2 Pt 2):R389–94.

    Not in our library10.1152/ajpregu.1995.268.2.r389

  115. 115.

    Madden CJ: Consumption of a high fat diet inhibits sympathetic outflow to brown adipose tissue (BAT) via vagal afferent activation of neurons in the Nucleus Tractus Solitarius (NTS). Auton Neurosci. 2015;192:13

    Not in our library10.1016/j.autneu.2015.07.288

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