Abstract
Temperature affects all aspects of life down to the diffusion rates of biologically active molecules and reaction rates of enzymes. The reciprocal argument holds true as well and every biological process down to enzymatic reactions influences temperature. In order to assure biological stability, mammalian organisms possess the remarkable ability to maintain internal body temperature within a narrow range, which in humans and mice is close to 37 °C, despite wide environmental temperature variations and different rates of internal heat production. Nevertheless, body temperature is not a static property but adaptively regulated upon physiological demands and in the context of pathological conditions. The brain region that has been primarily associated with internal temperature regulation is the preoptic area and the anterior portion of the hypothalamus. Similar to a thermostat, this brain area detects deep brain temperature, integrates temperature information from peripheral body sensors, and—based on these inputs––controls body temperature homeostasis. Discovered more than a century ago, we still know comparatively little about the molecular and cellular make-up of the hypothalamic thermoregulatory center. After a brief historic outline that led to the discovery of the thermoregulatory center, we here review recent studies that have considerably advanced our understanding of hypothalamic thermoregulation. We touch upon proposed mechanisms of intrinsic deep brain temperature detection and focus on newly identified hypothalamic cell populations that mediate thermoregulatory responses and that provide novel entry points not only to shed light on the mechanistic underpinnings of the thermoregulatory center but also to probe its therapeutic value.
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References
Abbott SB, Machado NL, Geerling JC, Saper CB (2016) Reciprocal control of drinking behavior by median preoptic neurons in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 36(31):8228–8237. https://doi.org/10.1523/JNEUROSCI.1244-16.2016
Abbott SBG, Saper CB (2017) Median preoptic glutamatergic neurons promote thermoregulatory heat loss and water consumption in mice. J Physiol 595(20):6569–6583. https://doi.org/10.1113/JP274667
Abe J, Okazawa M, Adachi R, Matsumura K, Kobayashi S (2003) Primary cold-sensitive neurons in acutely dissociated cells of rat hypothalamus. Neurosci Lett 342(1-2):29–32. https://doi.org/10.1016/S0304-3940(03)00239-8
Allen WE, DeNardo LA, Chen MZ, Liu CD, Loh KM, Fenno LE, Ramakrishnan C, Deisseroth K, Luo L (2017) Thirst-associated preoptic neurons encode an aversive motivational drive. Science 357(6356):1149–1155. https://doi.org/10.1126/science.aan6747
Allen WE, Luo L (2015) Intersectional illumination of neural circuit function. Neuron 85(5):889–892. https://doi.org/10.1016/j.neuron.2015.02.032
Aronsohn E, Sachs J (1885) Die Beziehungen des Gehirns zur Körperwärme und zum Fieber. Pflugers Arch Physiol 37(1):232–249. https://doi.org/10.1007/BF01752423
Barbour HG (1912) Die Wirkung unmittelbarer Erwärmung und Abkiühlung tier Wärmezentra auf die Körpertemperatur. Archiv f experiment Pathol u Pharmakol 70(1):1–26. https://doi.org/10.1007/BF01865333
Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D (2007) The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448(7150):204–208. https://doi.org/10.1038/nature05910
Boulant JA (1986) Single neuron studies and their usefulness in understanding thermoregulation. The Yale journal of biology and medicine 59(2):179–188
Boulant JA (2000) Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin Infect Dis 31(Suppl 5):S157–S161. https://doi.org/10.1086/317521
Boulant JA (2006) Counterpoint: heat-induced membrane depolarization of hypothalamic neurons: an unlikely mechanism of central thermosensitivity. American journal of physiology Regulatory, integrative and comparative physiology 290:R1481–R1484; discussion R1484
Boulant JA, Dean JB (1986) Temperature receptors in the central nervous system. Annu Rev Physiol 48(1):639–654. https://doi.org/10.1146/annurev.ph.48.030186.003231
Boulant JA, Hardy JD (1974) The effect of spinal and skin temperatures on the firing rate and thermosensitivity of preoptic neurones. J Physiol 240(3):639–660. https://doi.org/10.1113/jphysiol.1974.sp010627
Bratincsak A, Palkovits M (2005) Evidence that peripheral rather than intracranial thermal signals induce thermoregulation. Neuroscience 135(2):525–532. https://doi.org/10.1016/j.neuroscience.2005.06.028
Brock JA, McAllen RM (2016) Spinal cord thermosensitivity: an afferent phenomenon? Temperature 3(2):232–239. https://doi.org/10.1080/23328940.2016.1157665
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816–824. https://doi.org/10.1038/39807
Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, O'Donnell D, Nicoll RA, Shah NM, Julius D, Basbaum AI (2011) Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 31(13):5067–5077. https://doi.org/10.1523/JNEUROSCI.6451-10.2011
Chen XM, Hosono T, Yoda T, Fukuda Y, Kanosue K (1998) Efferent projection from the preoptic area for the control of non-shivering thermogenesis in rats. J Physiol 512(Pt 3):883–892. https://doi.org/10.1111/j.1469-7793.1998.883bd.x
Chung S, Weber F, Zhong P, Tan CL, Nguyen TN, Beier KT, Hormann N, Chang WC, Zhang Z, Do JP, Yao S, Krashes MJ, Tasic B, Cetin A, Zeng H, Knight ZA, Luo L, Dan Y (2017) Identification of preoptic sleep neurons using retrograde labelling and gene profiling. Nature 545(7655):477–481. https://doi.org/10.1038/nature22350
Ciura S, Liedtke W, Bourque CW (2011) Hypertonicity sensing in organum vasculosum lamina terminalis neurons: a mechanical process involving TRPV1 but not TRPV4. The Journal of neuroscience : the official journal of the Society for Neuroscience 31(41):14669–14676. https://doi.org/10.1523/JNEUROSCI.1420-11.2011
Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, Brownell S, Fabre V, Huitron-Resendiz S, Henriksen S, Zorrilla EP, de Lecea L, Bartfai T (2006) Transgenic mice with a reduced core body temperature have an increased life span. Science 314(5800):825–828. https://doi.org/10.1126/science.1132191
Crawshaw L, Grahn D, Wollmuth L, Simpson L (1985) Central nervous regulation of body temperature in vertebrates: comparative aspects. Pharmacol Ther 30(1):19–30. https://doi.org/10.1016/0163-7258(85)90045-2
Curras MC, Kelso SR, Boulant JA (1991) Intracellular analysis of inherent and synaptic activity in hypothalamic thermosensitive neurones in the rat. J Physiol 440(1):257–271. https://doi.org/10.1113/jphysiol.1991.sp018707
de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS 2nd, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A 95(1):322–327. https://doi.org/10.1073/pnas.95.1.322
de Velasco B, Erclik T, Shy D, Sclafani J, Lipshitz H, McInnes R, Hartenstein V (2007) Specification and development of the pars intercerebralis and pars lateralis, neuroendocrine command centers in the drosophila brain. Dev Biol 302(1):309–323. https://doi.org/10.1016/j.ydbio.2006.09.035
Delgado JM, Hanai T (1966) Intracerebral temperatures in free-moving cats. Am J Phys 211:755–769
Eberwine J, Bartfai T (2011) Single cell transcriptomics of hypothalamic warm sensitive neurons that control core body temperature and fever response: signaling asymmetry and an extension of chemical neuroanatomy. Pharmacol Ther 129(3):241–259. https://doi.org/10.1016/j.pharmthera.2010.09.010
Feketa VV, Marrelli SP (2015) Induction of therapeutic hypothermia by pharmacological modulation of temperature-sensitive TRP channels: theoretical framework and practical considerations. Temperature 2(2):244–257. https://doi.org/10.1080/23328940.2015.1024383
Frank SM, Raja SN, Bulcao CF, Goldstein DS (1999) Relative contribution of core and cutaneous temperatures to thermal comfort and autonomic responses in humans. J Appl Physiol 86(5):1588–1593. https://doi.org/10.1152/jappl.1999.86.5.1588
Fusco MM, Hardy JD, Hammel HT (1961) Interaction of central and peripheral factors in physiological temperature regulation. Am J Phys 200:572–580. https://doi.org/10.1152/ajplegacy.1961.200.3.572
Glotzbach SF, Heller HC (1984) Changes in the thermal characteristics of hypothalamic neurons during sleep and wakefulness. Brain Res 309(1):17–26. https://doi.org/10.1016/0006-8993(84)91006-0
Gordon CJ (2012) Thermal physiology of laboratory mice: defining thermoneutrality. J Therm Biol 37(8):654–685. https://doi.org/10.1016/j.jtherbio.2012.08.004
Gould SJ, Lewontin RC (1979) The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proceedings of the Royal Society of London Series B, Biological sciences 205(1161):581–598. https://doi.org/10.1098/rspb.1979.0086
Griffin JD, Boulant JA (1995) Temperature effects on membrane potential and input resistance in rat hypothalamic neurones. J Physiol 488(Pt 2):407–418. https://doi.org/10.1113/jphysiol.1995.sp020975
Hamada FN, Rosenzweig M, Kang K, Pulver SR, Ghezzi A, Jegla TJ, Garrity PA (2008) An internal thermal sensor controlling temperature preference in Drosophila. Nature 454(7201):217–220. https://doi.org/10.1038/nature07001
Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y (2002) LTRPC2 Ca2+−permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 9(1):163–173. https://doi.org/10.1016/S1097-2765(01)00438-5
Hardy JD, Hellon RF, Sutherland K (1964) Temperature-sensitive neurones in the dog’s hypothalamus. J Physiol 175(2):242–253. https://doi.org/10.1113/jphysiol.1964.sp007515
Hayward JN, Baker MA (1968) Role of cerebral arterial blood in regulation of brain temperature in monkey. Am J Phys 215:389–403. https://doi.org/10.1152/ajplegacy.1968.215.2.389
Heller HC, Crawshaw LI, Hammel HT (1978) The thermostat of vertebrate animals. Sci Am 239(102–110):112–103
Hellon RF (1986) Are single-unit recordings useful in understanding thermoregulation? The Yale journal of biology and medicine 59(2):197–203
Henker RA, Brown SD, Marion DW (1998) Comparison of brain temperature with bladder and rectal temperatures in adults with severe head injury. Neurosurgery 42(5):1071–1075. https://doi.org/10.1097/00006123-199805000-00071
Herbison AE (2016) Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. Nat Rev Endocrinol 12(8):452–466. https://doi.org/10.1038/nrendo.2016.70
Hori A, Minato K, Kobayashi S (1999) Warming-activated channels of warm-sensitive neurons in rat hypothalamic slices. Neurosci Lett 275(2):93–96. https://doi.org/10.1016/S0304-3940(99)00732-6
Hori T, Nakashima T, Kiyohara T, Shibata M, Hori N (1980) Effect of calcium removal on thermosensitivity of preoptic neurons in hypothalamic slices. Neurosci Lett 20(2):171–175. https://doi.org/10.1016/0304-3940(80)90141-X
Horvath TL, Warden CH, Hajos M, Lombardi A, Goglia F, Diano S (1999) Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers. The Journal of neuroscience : the official journal of the Society for Neuroscience 19(23):10417–10427
Jacobson FH, Squires RD (1970) Thermoregulatory responses of the cat to preoptic and environmental temperatures. Am J Phys 218:1575–1582
Janas S, Seghers F, Schakman O, Alsady M, Deen P, Vriens J, Tissir F, Nilius B, Loffing J, Gailly P, Devuyst O (2016) TRPV4 is associated with central rather than nephrogenic osmoregulation. Pflugers Archiv : European journal of physiology 468(9):1595–1607. https://doi.org/10.1007/s00424-016-1850-5
Kashio M, Sokabe T, Shintaku K, Uematsu T, Fukuta N, Kobayashi N, Mori Y, Tominaga M (2012) Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions. Proc Natl Acad Sci U S A 109(17):6745–6750. https://doi.org/10.1073/pnas.1114193109
Kelso SR, Boulant JA (1982) Effect of synaptic blockade on thermosensitive neurons in hypothalamic tissue slices. Am J Phys 243:R480–R490
Kelso SR, Perlmutter MN, Boulant JA (1982) Thermosensitive single-unit activity of in vitro hypothalamic slices. Am J Phys 242:R77–R84
Kiyatkin EA (2007) Brain temperature fluctuations during physiological and pathological conditions. Eur J Appl Physiol 101(1):3–17. https://doi.org/10.1007/s00421-007-0450-7
Kiyatkin EA (2010) Brain temperature homeostasis: physiological fluctuations and pathological shifts. Front Biosci 15(1):73–92. https://doi.org/10.2741/3608
Kiyatkin EA, Bae D (2008) Behavioral and brain temperature responses to salient environmental stimuli and intravenous cocaine in rats: effects of diazepam. Psychopharmacology 196(3):343–356. https://doi.org/10.1007/s00213-007-0965-y
Kiyatkin EA, Brown PL, Wise RA (2002) Brain temperature fluctuation: a reflection of functional neural activation. Eur J Neurosci 16(1):164–168. https://doi.org/10.1046/j.1460-9568.2002.02066.x
Kiyatkin EA, Mitchum RD Jr (2003) Fluctuations in brain temperature during sexual interaction in male rats: an approach for evaluating neural activity underlying motivated behavior. Neuroscience 119(4):1169–1183. https://doi.org/10.1016/S0306-4522(03)00222-7
Kobayashi S, Hori A, Matsumura K, Hosokawa H (2006) Point: heat-induced membrane depolarization of hypothalamic neurons: a putative mechanism of central thermosensitivity. American journal of physiology Regulatory, integrative and comparative physiology 290:R1479–R1480; discussion R1484. doi:https://doi.org/10.1152/ajpregu.00655.2005, 5
Kumar S, Hedges SB (1998) A molecular timescale for vertebrate evolution. Nature 392(6679):917–920. https://doi.org/10.1038/31927
Lazarus M, Yoshida K, Coppari R, Bass CE, Mochizuki T, Lowell BB, Saper CB (2007) EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses. Nat Neurosci 10(9):1131–1133. https://doi.org/10.1038/nn1949
Liedtke W, Friedman JM (2003) Abnormal osmotic regulation in trpv4-/- mice. Proc Natl Acad Sci U S A 100(23):13698–13703. https://doi.org/10.1073/pnas.1735416100
Madisen L, Garner AR, Shimaoka D, Chuong AS, Klapoetke NC, Li L, van der Bourg A, Niino Y, Egolf L, Monetti C, Gu H, Mills M, Cheng A, Tasic B, Nguyen TN, Sunkin SM, Benucci A, Nagy A, Miyawaki A, Helmchen F, Empson RM, Knopfel T, Boyden ES, Reid RC, Carandini M, Zeng H (2015) Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance. Neuron 85(5):942–958. https://doi.org/10.1016/j.neuron.2015.02.022
Magoun HW, Harrison F, Brobeck JR, Ranson SW (1938) Activation of heat loss mechanisms by local heating of the brain. J Neurophysiol 1:101
McAllen RM, Tanaka M, Ootsuka Y, McKinley MJ (2010) Multiple thermoregulatory effectors with independent central controls. Eur J Appl Physiol 109(1):27–33. https://doi.org/10.1007/s00421-009-1295-z
Mellergard P, Nordstrom CH (1990) Epidural temperature and possible intracerebral temperature gradients in man. Br J Neurosurg 4(1):31–38. https://doi.org/10.3109/02688699009000679
Mishra SK, Tisel SM, Orestes P, Bhangoo SK, Hoon MA (2011) TRPV1-lineage neurons are required for thermal sensation. EMBO J 30(3):582–593. https://doi.org/10.1038/emboj.2010.325
Mizuno A, Matsumoto N, Imai M, Suzuki M (2003) Impaired osmotic sensation in mice lacking TRPV4. American journal of physiology Cell physiology 285(1):C96–101. https://doi.org/10.1152/ajpcell.00559.2002
Morrison SF (2016) Central neural control of thermoregulation and brown adipose tissue. Autonomic neuroscience : basic & clinical 196:14–24. https://doi.org/10.1016/j.autneu.2016.02.010
Morrison SF, Nakamura K (2011) Central neural pathways for thermoregulation. Front Biosci (Landmark Ed) 16(1):74–104. https://doi.org/10.2741/3677
Nakayama T, Eisenman JS, Hardy JD (1961) Single unit activity of anterior hypothalamus during local heating. Science 134(3478):560–561. https://doi.org/10.1126/science.134.3478.560
Nakayama T, Hammel HT, Hardy JD, Eisenman JS (1963) Thermal stimulation of electrical activity of single units of preoptic region. Am J Phys 204:1122–1126. https://doi.org/10.1152/ajplegacy.1963.204.6.1122
Ni L, Bronk P, Chang EC, Lowell AM, Flam JO, Panzano VC, Theobald DL, Griffith LC, Garrity PA (2013) A gustatory receptor paralogue controls rapid warmth avoidance in drosophila. Nature 500(7464):580–584. https://doi.org/10.1038/nature12390
Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP, Scharenberg AM (2001) ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411(6837):595–599. https://doi.org/10.1038/35079100
Pierau FK, Sann H, Yakimova KS, Haug P (1998) Plasticity of hypothalamic temperature-sensitive neurons. Prog Brain Res 115:63–84. https://doi.org/10.1016/S0079-6123(08)62030-0
Prager-Khoutorsky M, Khoutorsky A, Bourque CW (2014) Unique interweaved microtubule scaffold mediates osmosensory transduction via physical interaction with TRPV1. Neuron 83(4):866–878. https://doi.org/10.1016/j.neuron.2014.07.023
Richet C (1884) Del L'influence des lesions du cerveau sur la temperature. Acad des Sci 98:295
Sano Y, Inamura K, Miyake A, Mochizuki S, Yokoi H, Matsushime H, Furuichi K (2001) Immunocyte Ca2+ influx system mediated by LTRPC2. Science 293(5533):1327–1330. https://doi.org/10.1126/science.1062473
Saper CB, Lowell BB (2014) The hypothalamus. Current biology : CB 24(23):R1111–R1116. https://doi.org/10.1016/j.cub.2014.10.023
Schmidt-Nielsen K (1997) Adaptation and Environment, 5th edition edn. Cambridge University Press, Cambridge
Serota HM, Gerard RW (1938) Localized thermal changes in the cat’s brain. J Neurophysiol 1:115–124
Shu DG, Morris SC, Han J, Zhang ZF, Yasui K, Janvier P, Chen L, Zhang XL, Liu JN, Li Y, Liu HQ (2003) Head and backbone of the Early Cambrian vertebrate Haikouichthys. Nature 421(6922):526–529. https://doi.org/10.1038/nature01264
Siesjo B (1978) Brain energy metabolism. Wiley, New York
Simon E (2006) Ion channel proteins in neuronal temperature transduction: from inferences to testable theories of deep-body thermosensitivity. American journal of physiology Regulatory, integrative and comparative physiology 291(3):R515–R517. https://doi.org/10.1152/ajpregu.00239.2006
Song K, Wang H, Kamm GB, Pohle J, de Castro RF, Heppenstall P, Wende H, Siemens J (2016) The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia. Science 353(6306):1393–1398. https://doi.org/10.1126/science.aaf7537
Sudbury JR, Bourque CW (2013) Dynamic and permissive roles of TRPV1 and TRPV4 channels for thermosensation in mouse supraoptic magnocellular neurosecretory neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 33(43):17160–17165. https://doi.org/10.1523/JNEUROSCI.1048-13.2013
Szymusiak R, Satinoff E (1982) Acute thermoregulatory effects of unilateral electrolytic lesions of the medial and lateral preoptic area in rats. Physiol Behav 28(1):161–170. https://doi.org/10.1016/0031-9384(82)90118-4
Tan CH, McNaughton PA (2016) The TRPM2 ion channel is required for sensitivity to warmth. Nature 536(7617):460–463. https://doi.org/10.1038/nature19074
Tan CL, Cooke EK, Leib DE, Lin YC, Daly GE, Zimmerman CA, Knight ZA (2016) Warm-sensitive neurons that control body temperature. Cell 167(1):47–59 e15. https://doi.org/10.1016/j.cell.2016.08.028
Tessmar-Raible K (2007) The evolution of neurosecretory centers in bilaterian forebrains: insights from protostomes. Semin Cell Dev Biol 18(4):492–501. https://doi.org/10.1016/j.semcdb.2007.04.007
Tessmar-Raible K, Raible F, Christodoulou F, Guy K, Rembold M, Hausen H, Arendt D (2007) Conserved sensory-neurosecretory cell types in annelid and fish forebrain: insights into hypothalamus evolution. Cell 129(7):1389–1400. https://doi.org/10.1016/j.cell.2007.04.041
Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21(3):531–543. https://doi.org/10.1016/S0896-6273(00)80564-4
Tosches MA, Arendt D (2013) The bilaterian forebrain: an evolutionary chimaera. Curr Opin Neurobiol 23(6):1080–1089. https://doi.org/10.1016/j.conb.2013.09.005
Voets T (2016) Warm feelings for TRPM2. Cell Res 26(11):1174–1175. https://doi.org/10.1038/cr.2016.121
Vriens J, Nilius B, Voets T (2014) Peripheral thermosensation in mammals. Nat Rev Neurosci 15(9):573–589. https://doi.org/10.1038/nrn3784
Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, Benoit M, Xue F, Janssens A, Kerselaers S, Oberwinkler J, Vennekens R, Gudermann T, Nilius B, Voets T (2011) TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron 70(3):482–494. https://doi.org/10.1016/j.neuron.2011.02.051
Wang H, Siemens J (2015) TRP ion channels in thermosensation, thermoregulation and metabolism. Temperature 2(2):178–187. https://doi.org/10.1080/23328940.2015.1040604
Wechselberger M, Wright CL, Bishop GA, Boulant JA (2006) Ionic channels and conductance-based models for hypothalamic neuronal thermosensitivity. American journal of physiology Regulatory, integrative and comparative physiology 291(3):R518–R529. https://doi.org/10.1152/ajpregu.00039.2006
Wehage E, Eisfeld J, Heiner I, Jungling E, Zitt C, Luckhoff A (2002) Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose. J Biol Chem 277(26):23150–23156. https://doi.org/10.1074/jbc.M112096200
Yakimova KS, Sann H, Pierau FK (1998) Effects of kappa and delta opioid agonists on activity and thermosensitivity of rat hypothalamic neurons. Brain Res 786(1-2):133–142. https://doi.org/10.1016/S0006-8993(97)01456-X
Yarmolinsky DA, Peng Y, Pogorzala LA, Rutlin M, Hoon MA, Zuker CS (2016) Coding and plasticity in the mammalian thermosensory system. Neuron 92(5):1079–1092. https://doi.org/10.1016/j.neuron.2016.10.021
Yu S, Qualls-Creekmore E, Rezai-Zadeh K, Jiang Y, Berthoud HR, Morrison CD, Derbenev AV, Zsombok A, Munzberg H (2016) Glutamatergic preoptic area neurons that express leptin receptors drive temperature-dependent body weight homeostasis. The Journal of neuroscience : the official journal of the Society for Neuroscience 36(18):5034–5046. https://doi.org/10.1523/JNEUROSCI.0213-16.2016
Zhao ZD, Yang WZ, Gao CC, Fu X, Zhang W, Zhou Q, Chen WP, Ni XY, Lin JK, Yang J, Xu XH, Shen WL (2017) A hypothalamic circuit that controls body temperature. P Natl Acad Sci USA 114(8):2042–2047. https://doi.org/10.1073/pnas.1616255114
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This article is part of the special issue on Thermal biology in Pflügers Archiv – European Journal of Physiology
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Siemens, J., Kamm, G.B. Cellular populations and thermosensing mechanisms of the hypothalamic thermoregulatory center. Pflugers Arch - Eur J Physiol 470, 809–822 (2018). https://doi.org/10.1007/s00424-017-2101-0
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DOI: https://doi.org/10.1007/s00424-017-2101-0