Role of the preoptic-anterior hypothalamus in thermoregulation and fever
Abstract
Lesion and thermal stimulation studies suggest that temperature regulation is controlled by a hierarchy of neural structures. Effector areas for specific thermoregulatory responses are located throughout the brain stem and spinal cord. The preoptic region, in and near the rostral hypothalamus, acts as a coordinating center and strongly influences each of the lower effector areas. The preoptic area contains neurons that are sensitive to subtle changes in hypothalamic or core temperature. Preoptic thermosensitive neurons also receive a wealth of somatosensory input from skin and spinal thermoreceptors. In this way, preoptic neurons compare and integrate central and peripheral thermal information. As a result of this sensory integration and its control over lower effector areas, the preoptic region elicits the thermoregulatory responses that are the most appropriate for both internal and environmental thermal conditions. Thermosensitive preoptic neurons are also affected by endogenous substances, such as pyrogens. By reducing the activity of warm-sensitive neurons and increasing the activity of cold-sensitive neurons, pyrogens cause fever, a state in which all thermoregulatory responses have elevated set-point temperatures.
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Autonomic thermoeffectors are controlled by neural pathways passing through the preoptic anterior hypothalamus, specifically through the MnPO and the medial preoptic area.
“Autonomic thermoeffectors are controlled by neural pathways passing through the preoptic anterior hypothalamus, specifically, through the MnPO and the medial preoptic area (Boulant, 2000; Romanovsky et al., 2009).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Boulant, 2000
Thermosensitive neurons that participate in physiological thermoregulation are predominantly warm-sensitive cells located mostly in the preoptic hypothalamus.
“Thermosensitive neurons that do participate in physiological thermoregulation are predominantly warm-sensitive cells located mostly in the preoptic hypothalamus (Boulant, 2000; Nakayama et al., 1961).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Boulant, 2000
Thermosensitive neurons receive information related to gonadal hormones, including estrogen.
“Thermosensitive neurons also receive information related to blood pressure, osmolarity, pyrogens, glucose concentration, and gonadal hormones, including estrogen (Boulant, 2000; Silva and Boulant, 1986).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Boulant, 2000
Cites
Advances in Comparative and Environmental Physiology
Houlihan, D. F., Livingstone, D. R., & Lee, R. F. (1991) · Advances in comparative and environmental physiology · doi:10.1007/978-3-642-75897-3 · Cited by 739 · see citing works
Physiological and behavioral temperature regulation
Hardy, J. D., GAGGE, A. P., & Stolwijk, J. A. J. (1970) · Thomas eBooks · Cited by 673 · see citing works
Morgane, P. J., & Panksepp, J. (1979) · M. Dekker eBooks · Cited by 497 · see citing works
Temperature Receptors in the Central Nervous System
Boulant, J. A., & Dean, J. B. (1986) · Annual Review of Physiology · doi:10.1146/annurev.ph.48.030186.003231 · Cited by 286 · see citing works
Self-citationACTIVATION OF HEAT LOSS MECHANISMS BY LOCAL HEATING OF THE BRAIN
Magoun, H. W., Harrison, F., Brobeck, J. R., & Ranson, S. W. (1938) · Journal of Neurophysiology · doi:10.1152/jn.1938.1.2.101 · Cited by 263 · see citing works
Thermal stimulation of electrical activity of single units of the preoptic region
Nakayama, T., Hammel, H. T., Hardy, J. D., & Eisenman, J. S. (1963) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1963.204.6.1122 · Cited by 260 · see citing works
Boulant, J. A., & Hardy, J. D. (1974) · The Journal of Physiology · doi:10.1113/jphysiol.1974.sp010627 · Cited by 241 · see citing works
Self-citationThermoregulatory responses to hypothalamic cooling in unanesthetized dogs
Hammel, H. T., Hardy, J. D., & Fusco, M. M. (1960) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1960.198.3.481 · Cited by 218 · see citing works
Prostaglandin E as the neural mediator of the febrile response.
Stitt, J. T. (1986) · PubMed · Cited by 197 · see citing works
Physiological Controls and Regulations.
(1966) · Annals of Internal Medicine · doi:10.7326/0003-4819-64-3-727_1 · Cited by 179 · see citing works
Physiological Controls and Regulations
Apter, J. T. (1966) · JAMA · doi:10.1001/jama.1966.03100170116053 · Cited by 142 · see citing works
Die Wirkung unmittelbarer Erwärmung und Abkühlung der Wärmezentra auf die Körpertemperatur
BARBOUR, H. G. (1912) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf01865333 · Cited by 127 · see citing works
Hypothalamic Neurons Regulating Body Temperature
Boulant, J. A. (1996) · Comprehensive physiology · doi:10.1002/cphy.cp040106 · Cited by 121 · see citing works
Self-citationSome characteristics of temperature regulation in the unanesthetized dog
Hellström, B., & Hammel, H. (1967) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1967.213.2.547 · Cited by 108 · see citing works
Effect of synaptic blockade on thermosensitive neurons in hypothalamic tissue slices
Kelso, S. R., & Boulant, J. A. (1982) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1982.243.5.r480 · Cited by 95 · see citing works
Self-citationMackowiak, P. A., & Boulant, J. A. (1996) · Clinical Infectious Diseases · doi:10.1093/clinids/22.3.525 · Cited by 93 · see citing works
Self-citationCellular mechanisms for neuronal thermosensitivity in the rat hypothalamus.
Griffin, J. D., Kaple, M. L., Chow, A., & Boulant, J. A. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021304 · Cited by 87 · see citing works
Self-citationCurrás, M. C., Kelso, S. R., & Boulant, J. A. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018707 · Cited by 85 · see citing works
Self-citationHypothalamic network for thermoregulatory vasomotor control
Kanosue, K., Yanase‐Fujiwara, M., & Hosono, T. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.1.r283 · Cited by 76 · see citing works
EFFECTS OF HEATING HYPOTHALAMUS OF DOGS BY DIATHERMY
Hemingway, A., Rasmussen, T., Wikoff, H. M., & Rasmussen, A. T. (1940) · Journal of Neurophysiology · doi:10.1152/jn.1940.3.4.329 · Cited by 71 · see citing works
In vitro localization of thermosensitive neurons in the rat diencephalon
Dean, J. B., & Boulant, J. A. (1989) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1989.257.1.r57 · Cited by 70 · see citing works
Self-citationContrd of Thyrotrophic Hormone (TSH) Secretion by the“Heat Loss Center”
Anderson, B. E., Ekman, L. G., GALE, C. C., et al. (1963) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1963.tb02719.x · Cited by 68 · see citing works
Thermosensitive single-unit activity of in vitro hypothalamic slices
Kelso, S. R., Perlmutter, M. N., & Boulant, J. A. (1982) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1982.242.1.r77 · Cited by 64 · see citing works
Self-citationEffects on cats of conductive hypothalamic cooling
Freeman, W. J., & Davis, D. D. (1959) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1959.197.1.145 · Cited by 63 · see citing works
Thermoregulatory responses of the cat to preoptic and environmental temperatures
Jacobson, F., & Squires, R. (1970) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1970.218.6.1575 · Cited by 59 · see citing works
The effect of skin temperature on the hypothalamic control of heat loss and heat production
Boulant, J. A., & Gonzalez, R. R. (1977) · Brain Research · doi:10.1016/0006-8993(77)90916-7 · Cited by 57 · see citing works
Self-citationNeurophysiological Aspects of Thermoregulation
Boulant, J. A., Currás, M. C., & Dean, J. B. (1989) · Advances in comparative and environmental physiology · doi:10.1007/978-3-642-74078-7_4 · Cited by 55 · see citing works
Self-citationSkin, preoptic, and core temperatures influence behavioral thermoregulation
Adair, E. R. (1977) · Journal of Applied Physiology · doi:10.1152/jappl.1977.42.4.559 · Cited by 53 · see citing works
Hypothalamic network for thermoregulatory shivering
Kanosue, K., Zhang, Y. H., Yanase‐Fujiwara, M., & Hosono, T. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.1.r275 · Cited by 52 · see citing works
Endocrine thermoregulatory responses to local hypothalamic cooling in unanesthetized baboons
Gale, C., Jobin, M., Proppe, D. W., Notter, D. R., & Fox, H. (1970) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1970.219.1.193 · Cited by 51 · see citing works
The central and the reflex mechanism of panting
Hammouda, M. (1933) · The Journal of Physiology · doi:10.1113/jphysiol.1933.sp002972 · Cited by 49 · see citing works
Pharmakologische und physiologische Studien über die Schweißzentren
Hasama, B.-I. (1929) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf01863269 · Cited by 48 · see citing works
Effects of synaptic blockade on thermosensitive neurons in rat diencephalon in vitro
Dean, J. B., & Boulant, J. A. (1989) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1989.257.1.r65 · Cited by 46 · see citing works
Self-citationThe central efferent mechanism of brown adipose tissue thermogenesis induced by preoptic cooling
Imai-Matsumura, K., & Nakayama, T. (1987) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y87-206 · Cited by 43 · see citing works
Intracellular Recordings from Thermosensitive Preoptic Neurons
Nelson, D. O., & Prosser, C. L. (1981) · Science · doi:10.1126/science.7256280 · Cited by 43 · see citing works
WANG, L. C. H. (1989) · Advances in comparative and environmental physiology · doi:10.1007/978-3-642-74078-7 · Cited by 39 · see citing works
HYPOTHALAMUS AND TEMPERATURE CONTROL
Bazett, H. C. (1933) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1933.02240160028002 · Cited by 38 · see citing works
Pharmakologische und physiologische Studien über die Schweißzentren
Hasama, B.-I. (1930) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf01862012 · Cited by 34 · see citing works
Andersson, B., GALE, C. C., HÖKFELT, B., et al. (1964) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1964.tb02954.x · Cited by 30 · see citing works
Die Beziehungen des Gehirns zur Körperwärme und zum Fieber
RICHET, C. (1885) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf01752446 · Cited by 28 · see citing works
EFFECT OF INCREASED TEMPERATURE OF THE CAROTID BLOOD
Moorhouse, V. H. K. (1911) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1911.28.4.223 · Cited by 27 · see citing works
Observations on the Localization in the Brain-stem of Mechanisms Controlling Body Temperature
Keller, A. D. (1933) · The American Journal of the Medical Sciences · doi:10.1097/00000441-193305000-00056 · Cited by 23 · see citing works
Evans, S., & Ingram, D. L. (1974) · The Journal of Physiology · doi:10.1113/jphysiol.1974.sp010428 · Cited by 12 · see citing works
Effects of changing hypothalamic temperature on eccrine sweating in the patas monkey
GISOLFI, C. V., Owen, M. D., Wall, P. T., & Kregel, K. C. (1988) · Brain Research Bulletin · doi:10.1016/0361-9230(88)90176-1 · Cited by 7 · see citing works
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CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433 · see citing works
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Kolarsick, P. A. J., Kolarsick, M. A., & Goodwin, C. (2011) · Journal of the Dermatology Nurses' Association · doi:10.1097/jdn.0b013e3182274a98 · Cited by 578 · see citing works
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Conti, B., Sanchez-Alavez, M., Winsky-Sommerer, R., Morale, M. C., Lucero, J., Brownell, S., Fabre, V., Huitron-Resendiz, S., Henriksen, S., Zorrilla, E. P., et al. (2006) · Science · doi:10.1126/science.1132191 · Cited by 392 · see citing works
Rance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.003 · Cited by 380 · see citing works
Burke, M. C., Letts, P. A., Krajewski, S. J., & Rance, N. E. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.21086 · Cited by 280 · see citing works
Relationships between sleep, physical activity and human health
Atkinson, G., & Davenne, D. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.09.015 · Cited by 267 · see citing works
Thermal pleasure in built environments: physiology of alliesthesia
Parkinson, T., & de Dear, R. (2015) · Building Research & Information · doi:10.1080/09613218.2015.989662 · Cited by 263 · see citing works
Menopausal hot flushes and night sweats: where are we now?
Archer, D. F., Sturdee, D. W., Baber, R., de Villiers, T. J., Pines, A., Freedman, R. R., Gompel, A., Hickey, M., Hunter, M. S., Lobo, R. A., et al. (2011) · Climacteric · doi:10.3109/13697137.2011.608596 · Cited by 185 · see citing works
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Feenstra, B., Pasternak, B., Geller, F., Carstensen, L., Wang, T., Huang, F., Eitson, J. L., Hollegaard, M. V., Svanström, H., Vestergaard, M., et al. (2014) · Nature Genetics · doi:10.1038/ng.3129 · Cited by 152 · see citing works
Geerling, J. J., Boon, M. R., Kooijman, S., Parlevliet, E. T., Havekes, L. M., Romijn, J. A., Meurs, I. M., & Rensen, P. C. N. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r045013 · Cited by 137 · see citing works
Kiyatkin, E. A. (2019) · Temperature · doi:10.1080/23328940.2019.1691896 · Cited by 122 · see citing works
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Li, S., Dou, W., Tang, Y., Goorha, S., Ballou, L. R., & Blatteis, C. M. (2008) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2007.10.007 · Cited by 63 · see citing works
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Kanashiro, A., Pessini, A. C., Machado, R. R., Malvar, D. D. C., Aguiar, F. A., Soares, D. M., do Vale, M. L., & de Souza, G. E. P. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90527.2008 · Cited by 41 · see citing works
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- Authors
- Boulant, J. A.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Boulant, Jack A.
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-10-01
- Volume
- 31
- Issue
- Supplement_5
- Pages
- S157-S161
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2105303099
- Cited by
- 562
- References
- 44
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 23 · 2023: 18 · 2022: 10 · 2021: 27 · 2020: 26 · 2019: 21 · 2018: 32 · 2017: 28 · 2016: 22 · 2015: 20 · 2014: 29 · 2013: 20 · 2012: 19
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS014644, NS14644)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- preoptic area, anterior hypothalamus, thermoregulation, fever, thermosensitive neurons, pyrogens, setpoint temperature, cold-sensitive neurons, warm-sensitive neurons
- MeSH terms
- Body Temperature Regulation, Fever, Humans, Hypothalamus, Anterior, Neurons, Preoptic Area
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