Warm-Sensitive Neurons that Control Body Temperature
Open accessAbstract
Thermoregulation is one of the most vital functions of the brain, but how temperature information is converted into homeostatic responses remains unknown. Here, we use an unbiased approach for activity-dependent RNA sequencing to identify warm-sensitive neurons (WSNs) within the preoptic hypothalamus that orchestrate the homeostatic response to heat. We show that these WSNs are molecularly defined by co-expression of the neuropeptides BDNF and PACAP. Optical recordings in awake, behaving mice reveal that these neurons are selectively activated by environmental warmth. Optogenetic excitation of WSNs triggers rapid hypothermia, mediated by reciprocal changes in heat production and loss, as well as dramatic cold-seeking behavior. Projection-specific manipulations demonstrate that these distinct effectors are controlled by anatomically segregated pathways. These findings reveal a molecularly defined cell type that coordinates the diverse behavioral and autonomic responses to heat. Identification of these warm-sensitive cells provides genetic access to the core neural circuit regulating the body temperature of mammals. PAPERCLIP.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Warm-sensitive neurons in the preoptic area of the hypothalamus integrate temperature information from the periphery and control some of the many signals that affect thermogenesis.
“Warm-sensitive neurons in the preoptic area of the hypothalamus integrate temperature information from the periphery and control some of the many signals that affect thermogenesis (79).”
From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [79]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The capsaicin receptor: a heat-activated ion channel in the pain pathway
Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., & Julius, D. J. (1997) · Nature · doi:10.1038/39807 · Cited by 9,132 · see citing works
Identification of a cold receptor reveals a general role for TRP channels in thermosensation
McKemy, D. D., Neuhausser, W., & Julius, D. J. (2002) · Nature · doi:10.1038/nature719 · Cited by 2,716 · see citing works
Neocortical excitation/inhibition balance in information processing and social dysfunction
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., et al. (2011) · Nature · doi:10.1038/nature10360 · Cited by 2,454 · see citing works
Natural neural projection dynamics underlying social behavior
Gunaydin, L. A., Grosenick, L., Finkelstein, J. C., Kauvar, I. V., Fenno, L. E., Adhikari, A., Lammel, S., Mirzabekov, J. J., Airan, R. D., Zalocusky, K. A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.017 · Cited by 1,389 · see citing works
Broberger, C., Johansen, J., Johansson, C., Schalling, M., & Hökfelt, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15043 · Cited by 798 · see citing works
Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system
Romanovsky, A. A. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00668.2006 · Cited by 786 · see citing works
Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits
Chen, Y., Lin, Y.-C., Kuo, T.-W., & Knight, Z. A. (2015) · Cell · doi:10.1016/j.cell.2015.01.033 · Cited by 660 · see citing works
Self-citationCentral neural pathways for thermoregulation
Shaun, F. M. (2010) · Frontiers in bioscience · doi:10.2741/3677 · Cited by 658 · see citing works
Regulation of Internal Body Temperature
Hammel, H. T., & Pierce, J. B. (1968) · Annual Review of Physiology · doi:10.1146/annurev.ph.30.030168.003233 · Cited by 626 · see citing works
Galanin neurons in the medial preoptic area govern parental behaviour
Wu, Z., Autry, A. E., Bergan, J. F., Watabe‐Uchida, M., & Dulac, C. G. (2014) · Nature · doi:10.1038/nature13307 · Cited by 592 · see citing works
Neural Organization and Evolution of Thermal Regulation in Mammals
Satinoff, E. (1978) · Science · doi:10.1126/science.351802 · Cited by 516 · see citing works
A thermosensory pathway that controls body temperature
Nakamura, K., & Morrison, S. F. (2007) · Nature Neuroscience · doi:10.1038/nn2027 · Cited by 503 · see citing works
Cell type–specific mRNA purification by translating ribosome affinity purification (TRAP)
Heiman, M., Kulicke, R., Fenster, R. J., Greengard, P., & Heintz, N. (2014) · Nature Protocols · doi:10.1038/nprot.2014.085 · Cited by 498 · see citing works
Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation
Harris, J. A., Hirokawa, K. E., Sorensen, S. A., Gu, H., Mills, M., Ng, L. L., Bohn, P., Mortrud, M., Ouellette, B., Kidney, J., et al. (2014) · Frontiers in Neural Circuits · doi:10.3389/fncir.2014.00076 · Cited by 485 · see citing works
Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus
Lee, H., Kim, D.-W., Remedios, R., Anthony, T. E., Chang, A., Madisen, L., Zeng, H., & Anderson, D. J. (2014) · Nature · doi:10.1038/nature13169 · Cited by 479 · see citing works
Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure
Morrison, S. F., Madden, C. J., & Tupone, D. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.007 · Cited by 427 · see citing works
Modeling the Spatiotemporal Dynamics of Light and Heat Propagation for In Vivo Optogenetics
Stujenske, J. M., Spellman, T., & Gordon, J. A. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.036 · Cited by 390 · see citing works
Molecular Profiling of Activated Neurons by Phosphorylated Ribosome Capture
Knight, Z. A., Tan, K., Birsoy, K., Schmidt, S. F., Garrison, J. L., Wysocki, R. W., Emiliano, A. B., Ekstrand, M. I., & Friedman, J. M. (2012) · Cell · doi:10.1016/j.cell.2012.10.039 · Cited by 312 · see citing works
Self-citationThe dorsomedial hypothalamus: a new player in thermoregulation
DiMicco, J. A., & Zaretsky, D. V. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00498.2006 · Cited by 300 · see citing works
Neuronal circuitries involved in thermoregulation
Nagashima, K., Nakai, S., Tanaka, M., & Kanosue, K. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00216-2 · Cited by 279 · see citing works
Suter, K. J. (2000) · Endocrinology · doi:10.1210/en.141.1.412 · Cited by 270 · see citing works
A thermosensory pathway mediating heat-defense responses
Nakamura, K., & Morrison, S. F. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913358107 · Cited by 267 · see citing works
ACTIVATION 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
A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion
Scott, N., Prigge, M., Yizhar, O., & Kimchi, T. (2015) · Nature · doi:10.1038/nature15378 · Cited by 261 · see citing works
Nakamura, K., & Morrison, S. F. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00427.2006 · Cited by 242 · 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
Zhang, Y., Kerman, I. A., Laque, A., Nguyen, P., Faouzi, M., Louis, G. W., Jones, J. C., Rhodes, C. J., & Münzberg, H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3223-10.2011 · Cited by 240 · see citing works
Kataoka, N., Hioki, H., Kaneko, T., & Nakamura, K. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.018 · Cited by 240 · see citing works
Suter, K. J., Song, W. J., Sampson, T. L., Wuarin, J., Saunders, J. T., Dudek, F. E., & Moenter, S. M. (2000) · Endocrinology · doi:10.1210/endo.141.1.7279 · Cited by 223 · see citing works
Cao, W.-H., Fan, W., & Morrison, S. F. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.013 · Cited by 221 · see citing works
Single unit activity of anterior hypothalamus during local heating
Nakayama, T., Eisenman, J. S., & Hardy, J. D. (1961) · Science · doi:10.1126/science.134.3478.560 · Cited by 214 · see citing works
Weiss, B., & Laties, V. G. (1961) · Science · doi:10.1126/science.133.3461.1338 · Cited by 198 · see citing works
Nest Building as an Indicator of Health and Welfare in Laboratory Mice
Gaskill, B. N., Karas, A. Z., Garner, J. P., & Pritchett‐Corning, K. R. (2013) · Journal of Visualized Experiments · doi:10.3791/51012 · Cited by 195 · see citing works
Temperature‐sensitive neurones in the dog's hypothalamus
Hardy, J. D., Hellon, R. F., & Sutherland, K. (1964) · The Journal of Physiology · doi:10.1113/jphysiol.1964.sp007515 · Cited by 182 · see citing works
McKinley, M. J., Yao, S. T., Uschakov, A., McAllen, R. M., Rundgren, M., & Martelli, D. (2015) · Acta Physiologica · doi:10.1111/apha.12487 · Cited by 180 · see citing works
Zaretskaia, M. V., Zaretsky, D. V., Shekhar, A., & DiMicco, J. A. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03369-8 · Cited by 173 · see citing works
Nakamura, Y., Nakamura, K., Matsumura, K., Kobayashi, S., Kaneko, T., & Morrison, S. F. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04515.x · Cited by 169 · see citing works
Unstressing intemperate models: how cold stress undermines mouse modeling
Karp, C. L. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120988 · Cited by 161 · see citing works
Thermoregulatory Phenotype of the Trpv1 Knockout Mouse: Thermoeffector Dysbalance with Hyperkinesis
Garami, A., Pákai, E., de Oliveira, D. L., Steiner, A. A., Wanner, S. P., Almeida, M. C., Lesnikov, V. A., Gavva, N. R., & Romanovsky, A. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4671-10.2011 · Cited by 140 · see citing works
Behavioral thermoregulation in rats with anterior hypothalamic lesions.
Satinoff, E., & Rutstein, J. E. (1970) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0028959 · Cited by 122 · see citing works
HYPOTHALAMIC REGULATION OF BODY TEMPERATURE
Clark, G. A., Magoun, H. W., & Ranson, S. W. (1939) · Journal of Neurophysiology · doi:10.1152/jn.1939.2.1.61 · Cited by 120 · see citing works
Genetic identity of thermosensory relay neurons in the lateral parabrachial nucleus
Geerling, J. C., Kim, M., Mahoney, C. E., Abbott, S. B. G., Agostinelli, L. J., Garfield, A. S., Krashes, M. J., Lowell, B. B., & Scammell, T. E. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00094.2015 · Cited by 118 · see citing works
Relationship between autonomic and behavioral thermoregulation in the mouse
Gordon, C. J. (1985) · Physiology & Behavior · doi:10.1016/0031-9384(85)90365-8 · Cited by 116 · see citing works
Multiple thermoregulatory effectors with independent central controls
McAllen, R. M., Tanaka, M., Ootsuka, Y., & McKinley, M. J. (2009) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1295-z · Cited by 112 · see citing works
Some 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
Crane, J. D., Mottillo, E. P., Farncombe, T. H., Morrison, K. M., & Steinberg, G. R. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.04.007 · Cited by 104 · see citing works
Effect of preoptic and anterior hypothalamic lesions on behavioral thermoregulation in the cold.
Carlisle, H. J. (1969) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0028170 · Cited by 94 · see citing works
Hyperthermia induces c-fos expression in the preoptic area
Scammell, T. E., Price, K., & Sagar, S. M. (1993) · Brain Research · doi:10.1016/0006-8993(93)91280-6 · Cited by 94 · see citing works
Yoshida-Court, K., Konishi, M., Nagashima, K., Saper, C. B., & Kanosue, K. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.03.044 · Cited by 93 · see citing works
Nest Building as an Indicator of Health and Welfare in Laboratory Mice
Gaskill, B. N., Karas, A. Z., Garner, J. P., & Pritchett‐Corning, K. R. (2013) · Journal of Visualized Experiments · doi:10.3791/51012-v · Cited by 88 · see citing works
Neurosciences - From Molecule to Behavior: a university textbook
Galizia, C. G., & Lledo, P.-M. (2013) · Springer eBooks · doi:10.1007/978-3-642-10769-6 · Cited by 87 · see citing works
Behavioural Significance of Hypothalamic Temperature-Sensitive Cells
Carlisle, H. J. (1966) · Nature · doi:10.1038/2091324a0 · Cited by 63 · see citing works
Evidence that peripheral rather than intracranial thermal signals induce thermoregulation
Bratincsák, A., & Palkovits, M. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.06.028 · Cited by 63 · see citing works
THE ROLE OF THE ANTERIOR HYPOTHALAMUS IN TEMPERATURE REGULATION
Teague, R. S., & Ranson, S. W. (1936) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1936.117.3.562 · Cited by 56 · see citing works
Relationship Between Hypothalamic Temperature and Thermoregulatory Effectors in Unanesthetized Cat
Forster, R., & Ferguson, T. B. (1952) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1952.169.2.255 · Cited by 56 · see citing works
Sakurada, S., Shido, O., FUJIKAKE, K., & Nagasaka, T. (1993) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.43.659 · Cited by 42 · see citing works
McKinley, M. J., McAllen, R. M., Davern, P. J., Giles, M., Penschow, J., Sunn, N., Uschakov, A., & Oldfield, B. J. (2003) · Cited by 27 · see citing works
Are single-unit recordings useful in understanding thermoregulation?
Hellon, R. F. (1986) · PubMed Central · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region
Moffitt, J. R., Bambah-Mukku, D., Eichhorn, S. W., Vaughn, E., Shekhar, K., Perez, J. D., Rubinstein, N. D., Hao, J., Regev, A., Dulac, C., et al. (2018) · Science · doi:10.1126/science.aau5324 · Cited by 1,365 · see citing works
Regulation of Body Temperature by the Nervous System
Tan, C. L., & Knight, Z. A. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.022 · Cited by 798 · see citing works
Self-citationNeural circuit mechanisms of social behavior
Chen, P., & Hong, W. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.026 · Cited by 527 · see citing works
Central Mechanisms for Thermoregulation
Morrison, S. F., & Nakamura, K. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114546 · Cited by 577 · see citing works
Human temperature regulation under heat stress in health, disease, and injury
Cramer, M. N., Gagnon, D., Laitano, O., & Crandall, C. G. (2022) · Physiological Reviews · doi:10.1152/physrev.00047.2021 · Cited by 537 · see citing works
A TRP channel trio mediates acute noxious heat sensing
Vandewauw, I., Clercq, K. D., Mulier, M., Held, K., Pinto, S., Ranst, N. V., Segal, A., Voet, T., Vennekens, R., Zimmermann, K., et al. (2018) · Nature · doi:10.1038/nature26137 · Cited by 473 · see citing works
Classic and exertional heatstroke
Bouchama, A., Abuyassin, B., Lehé, C. L., Laitano, O., Jay, O., O’Connor, F. G., & Leon, L. R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00334-6 · Cited by 476 · see citing works
Thirst-associated preoptic neurons encode an aversive motivational drive.
Allen, W. E., DeNardo, L. A., Chen, M. Z., Liu, C. D., Loh, K. M., Fenno, L. E., Ramakrishnan, C., Deisseroth, K., & Luo, L. (2017) · Science · doi:10.1126/science.aan6747 · Cited by 390 · see citing works
An evolutionary perspective on immunometabolism
Wang, A., Luan, H. H., & Medzhitov, R. M. (2019) · Science · doi:10.1126/science.aar3932 · Cited by 387 · see citing works
A hypothalamic circuit that controls body temperature
Zhao, Z., Yang, W. Z., Gao, C., Fu, X., Zhang, W., Zhou, Q., Chen, W., Ni, X., Lin, J.-K., Yang, J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616255114 · Cited by 352 · see citing works
Non-invasive transcranial ultrasound stimulation for neuromodulation
Darmani, G., Bergmann, T. O., Pauly, K. B., Caskey, C. F., de Lecea, L., Fomenko, A., Fouragnan, E. F., Legon, W., Murphy, K. R., Nandi, T., et al. (2021) · Clinical Neurophysiology · doi:10.1016/j.clinph.2021.12.010 · Cited by 335 · see citing works
Gut-Brain Cross-Talk in Metabolic Control
Clemmensen, C., Müller, T. D., Woods, S. C., Berthoud, H., Seeley, R. J., & Tschöp, M. H. (2017) · Cell · doi:10.1016/j.cell.2017.01.025 · Cited by 296 · see citing works
Neurons that regulate mouse torpor
Hrvatin, S., Sun, S., Wilcox, O. F., Yao, H., Lavin-Peter, A. J., Cicconet, M., Assad, E. G., Palmer, M. E., Aronson, S., Banks, A. S., et al. (2020) · Nature · doi:10.1038/s41586-020-2387-5 · Cited by 291 · see citing works
Deficiency of TRPM2 leads to embryonic neurogenesis defects in hyperthermia
Li, Y., & Jiao, J. (2020) · Science Advances · doi:10.1126/sciadv.aay6350 · Cited by 290 · see citing works
The form and function of channelrhodopsin
Deisseroth, K. A., & Hegemann, P. (2017) · Science · doi:10.1126/science.aan5544 · Cited by 281 · see citing works
Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice
Kroeger, D., Absi, G., Gagliardi, C., Bandaru, S. S., Madara, J. C., Ferrari, L. L., Arrigoni, E., Münzberg, H., Scammell, T. E., Saper, C. B., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06590-7 · Cited by 276 · see citing works
Allostasis: A brain-centered, predictive mode of physiological regulation
Schulkin, J., & Sterling, P. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.07.010 · Cited by 265 · see citing works
A discrete neuronal circuit induces a hibernation-like state in rodents
Takahashi, T. M., Sunagawa, G. A., Soya, S., Abe, M., Sakurai, K., Ishikawa, K., Yanagisawa, M., Hama, H., Hasegawa, E., Miyawaki, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2163-6 · Cited by 263 · see citing works
The Temperature Dependence of Sleep
Harding, E. C., Franks, N. P., & Wisden, W. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00336 · Cited by 261 · see citing works
“PACAP/BDNF, TRPM2-glutamate and nitrergicglutamate neurons are associated with warm-defence and fever but many other subpopulations exist (Song et al., 2016; Tan et al., 2016; Harding et al., 2018).”
BackgroundInfluentialEstimation of Current and Future Physiological States in Insular Cortex
Livneh, Y., Sugden, A. U., Madara, J. C., Essner, R. A., Flores, V. I., Sugden, L. A., Resch, J. M., Lowell, B. B., & Andermann, M. L. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.027 · Cited by 209 · see citing works
Neural Mechanisms of Inflammation-Induced Fever
Blomqvist, A. G., & Engblom, D. (2018) · The Neuroscientist · doi:10.1177/1073858418760481 · Cited by 197 · see citing works
Physiological and Behavioral Mechanisms of Thermoregulation in Mammals
Mota‐Rojas, D., Titto, C. G., Orihuela, A., Martı́nez-Burnes, J., Gómez-Prado, J., Torres-Bernal, F., Flores-Padilla, K., la Fuente, V. C.-D., & Wang, D. (2021) · Animals · doi:10.3390/ani11061733 · Cited by 209 · see citing works
The thermoregulation system and how it works
(2018) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-63912-7.00001-1 · Cited by 186 · see citing works
Gao, C., Leng, Y., Ma, J., Rooke, V., Rodriguez-Gonzalez, S., Ramakrishnan, C., Deisseroth, K. A., & Penzo, M. A. (2020) · Nature Neuroscience · doi:10.1038/s41593-019-0572-3 · Cited by 180 · see citing works
A preoptic neuronal population controls fever and appetite during sickness
Osterhout, J. A., Kapoor, V., Eichhorn, S. W., Vaughn, E., Moore, J. D., Liu, D., Lee, D., DeNardo, L. A., Luo, L., Zhuang, X., et al. (2022) · Nature · doi:10.1038/s41586-022-04793-z · Cited by 179 · see citing works
The neural basis of homeostatic and anticipatory thirst
Gizowski, C., & Bourque, C. W. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.149 · Cited by 173 · see citing works
Central nervous system circuits that control body temperature
Madden, C. J., & Morrison, S. F. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.11.027 · Cited by 171 · see citing works
A Neural Circuit Underlying the Generation of Hot Flushes
Padilla, S. L., Johnson, C. W., Barker, F. D., Patterson, M. A., & Palmiter, R. D. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.037 · Cited by 166 · see citing works
Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons
Zhang, K. X., D’Souza, S., Upton, B. A., Kernodle, S., Vemaraju, S., Nayak, G., Gaitonde, K. D., Holt, A. L., Linne, C. D., Smith, A. N., et al. (2020) · Nature · doi:10.1038/s41586-020-2683-0 · Cited by 154 · see citing works
STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury
Paris, A. J., Hayer, K. E., Oved, J. H., Avgousti, D. C., Toulmin, S. A., Zepp, J. A., Zacharias, W. J., Katzen, J. B., Basil, M. C., Kremp, M. M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0569-x · Cited by 148 · see citing works
The neural circuitry of social homeostasis: Consequences of acute versus chronic social isolation
Lee, C. R., Chen, A., & Tye, K. M. (2021) · Cell · doi:10.1016/j.cell.2021.02.028 · Cited by 138 · see citing works
The paraventricular nucleus of the thalamus: an integrative node underlying homeostatic behavior
Penzo, M. A., & Gao, C. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.03.001 · Cited by 138 · see citing works
Neural control of parental behaviors
Kohl, J., & Dulac, C. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.002 · Cited by 136 · see citing works
A neuronal hub binding sleep initiation and body cooling in response to a warm external stimulus
Harding, E. C., Yu, X., Miao, A., Andrews, N., Ma, Y., Ye, Z., Lignos, L., Miracca, G., Ba, W., Yustos, R., et al. (2018) · Current Biology · doi:10.1016/j.cub.2018.05.054 · Cited by 136 · see citing works
Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice
Zhang, Z., Reis, F. M., He, Y., Park, J. W., DiVittorio, J. R., Sivakumar, N., van Veen, J. E., Maesta‐Pereira, S., Shum, M., Nichols, I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20050-1 · Cited by 138 · see citing works
Galanin Neurons Unite Sleep Homeostasis and α2-Adrenergic Sedation
Ma, Y., Miracca, G., Yu, X., Harding, E. C., Miao, A., Yustos, R., Vyssotski, A. L., Franks, N. P., & Wisden, W. (2019) · Current Biology · doi:10.1016/j.cub.2019.07.087 · Cited by 126 · see citing works
The Forebrain Thirst Circuit Drives Drinking through Negative Reinforcement
Leib, D. E., Zimmerman, C. A., Poormoghaddam, A., Huey, E. L., Ahn, J. S., Lin, Y.-C., Tan, C. L., Chen, Y., & Knight, Z. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.041 · Cited by 128 · see citing works
Self-citationA Ca2+-sensor switch for tolerance to elevated salt stress in Arabidopsis
Steinhorst, L., He, G., Moore, L. K., Schültke, S., Schmitz-Thom, I., Cao, Y., Hashimoto, K., Andrés, Z., Piepenburg, K., Ragel, P., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.08.001 · Cited by 123 · see citing works
A hypothalamomedullary network for physiological responses to environmental stresses
Nakamura, K., Nakamura, Y., & Kataoka, N. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00532-x · Cited by 120 · see citing works
Bader, S. B., Dewhirst, M. W., & Hammond, E. M. (2020) · Cancers · doi:10.3390/cancers13010023 · Cited by 120 · see citing works
Yahiro, T., Kataoka, N., Nakamura, Y., & Nakamura, K. (2017) · Scientific Reports · doi:10.1038/s41598-017-05327-8 · Cited by 113 · see citing works
Multiple convergent hypothalamus–brainstem circuits drive defensive behavior
Lovett-Barron, M., Chen, R., Bradbury, S., Andalman, A. S., Wagle, M. D., Guo, S., & Deisseroth, K. A. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0655-1 · Cited by 110 · see citing works
A functional subdivision within the somatosensory system and its implications for pain research
Ma, Q. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.015 · Cited by 109 · see citing works
Piñol, R. A., Zahler, S. H., Li, C., Saha, A., Tan, B. K., Škop, V., Gavrilova, O., Xiao, C., Krashes, M. J., & Reitman, M. L. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0249-3 · Cited by 99 · see citing works
Livneh, Y., & Andermann, M. L. (2021) · Neuron · doi:10.1016/j.neuron.2021.08.036 · Cited by 106 · see citing works
Role of the Preoptic Area in Sleep and Thermoregulation
Rothhaas, R., & Chung, S. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.664781 · Cited by 98 · see citing works
Integrating Hunger with Rival Motivations
Hickey, A. K. S., & Krashes, M. J. (2020) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.04.006 · Cited by 95 · see citing works
Regulation of Energy Expenditure by Brainstem GABA Neurons
Schneeberger, M., Parolari, L., Banerjee, T. D., Bhave, V. M., Wang, P., Patel, B., Topilko, T., Wu, Z., Choi, C. H. J., Yu, X., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.048 · Cited by 96 · see citing works
Effects of thyroid hormones on thermogenesis and energy partitioning
Iwen, K. A., Oelkrug, R., & Brabant, G. E. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0319 · Cited by 97 · see citing works
Metabolic homeostasis via BDNF and its receptors
Podyma, B., Parekh, K., Güler, A. D., & Deppmann, C. D. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.04.005 · Cited by 92 · see citing works
Interactions between central nervous system and peripheral metabolic organs
Zeng, W., Yang, F., Shen, W. L., Zhan, C., Zheng, P., & Hu, J. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2103-5 · Cited by 96 · see citing works
A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors
Shi, G., Xing, L., Wu, D., Bhattacharyya, B. J., Jones, C. R., McMahon, T., Chong, S. Y. C., Chen, J., Coppola, G., Geschwind, D. H., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.07.026 · Cited by 90 · see citing works
EP3R-Expressing Glutamatergic Preoptic Neurons Mediate Inflammatory Fever
Machado, N., Bandaru, S. S., Abbott, S. B. G., & Saper, C. B. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2887-19.2020 · Cited by 86 · see citing works
Parabrachial neuron types categorically encode thermoregulation variables during heat defense
Yang, W. Z., Du, X., Zhang, W., Gao, C., Xie, H., Xiao, Y., Jia, X., Liu, J., Xu, J., Fu, X., et al. (2020) · Science Advances · doi:10.1126/sciadv.abb9414 · Cited by 80 · see citing works
Neurogenetic basis for circadian regulation of metabolism by the hypothalamusPreprint
Cedernaes, J., Waldeck, N. J., & Bass, J. T. (2019) · Genes & Development · doi:10.1101/gad.328633.119 · Cited by 84 · see citing works
Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways
Piñol, R. A., Mogul, A. S., Hadley, C. K., Saha, A., Li, C., Škop, V., Province, H. S., Xiao, C., Gavrilova, O., Krashes, M. J., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.05.001 · Cited by 76 · see citing works
Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area
Wang, T. A., Teo, C. F., Åkerblom, M., Chen, C., Fontaine, M. T.-L., Greiner, V. J., Diaz, A. A., McManus, M. T., Jan, Y. N., & Jan, L. Y. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.035 · Cited by 74 · see citing works
Abbott, S. B. G., & Saper, C. B. (2017) · The Journal of Physiology · doi:10.1113/jp274667 · Cited by 74 · see citing works
Sterling, P. (2020) · The MIT Press eBooks · doi:10.7551/mitpress/11472.001.0001 · Cited by 117 · see citing works
AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building
Li, X., Han, Y., Zhang, W., Wang, S.-R., Wei, Y., Li, S., Lin, J.-K., Yan, J.-J., Chen, A.-X., Zhang, X., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0958-18.2018 · Cited by 71 · see citing works
The TRPM2 channel: A thermo-sensitive metabolic sensor
Kashio, M., & Tominaga, M. (2017) · Channels · doi:10.1080/19336950.2017.1344801 · Cited by 70 · see citing works
The Effects of Estrogens on Neural Circuits That Control Temperature
Zhang, Z., DiVittorio, J. R., Joseph, A., & Correa, S. M. (2021) · Endocrinology · doi:10.1210/endocr/bqab087 · Cited by 70 · see citing works
Mota‐Rojas, D., Wang, D., Titto, C. G., Gómez-Prado, J., la Fuente, V. C.-D., Ghezzi, M. D., Boscato-Funes, L., Barrios-García, H., Torres-Bernal, F., Casas-Alvarado, A., et al. (2021) · Animals · doi:10.3390/ani11082316 · Cited by 69 · see citing works
Integrating Competing Demands of Osmoregulatory and Thermoregulatory Homeostasis
McKinley, M. J., Martelli, D., Pennington, G. L., Trevaks, D., & McAllen, R. M. (2018) · Physiology · doi:10.1152/physiol.00037.2017 · Cited by 67 · see citing works
A synaptic temperature sensor for body cooling
Kamm, G. B., Boffi, J. C., Zuza, K., Nencini, S., Campos, J., Schrenk-Siemens, K., Sonntag, I., Kabaoğlu, B., Hay, M. Y. A. E., Schwarz, Y. N., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.10.001 · Cited by 66 · see citing works
Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits
Ordás, P., Hernández‐Ortego, P., Vara, H., Fernández‐Peña, C., Reimúndez, A., Morenilla‐Palao, C., Guadaño‐Ferraz, A., Gomis, A., Hoon, M. A., Viana, F., et al. (2019) · The Journal of Comparative Neurology · doi:10.1002/cne.24694 · Cited by 65 · see citing works
The Sleep-Promoting Ventrolateral Preoptic Nucleus: What Have We Learned over the Past 25 Years?
Arrigoni, E., & Fuller, P. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23062905 · Cited by 66 · see citing works
Machado, N., Abbott, S. B. G., Resch, J. M., Zhu, L., Arrigoni, E., Lowell, B. B., Fuller, P. M., Fontes, M. A. P., & Saper, C. B. (2018) · Current Biology · doi:10.1016/j.cub.2018.05.064 · Cited by 63 · see citing works
Komagata, N., Latifi, B., Rusterholz, T., Bassetti, C. L., Adamantidis, A., & Schmidt, M. H. (2019) · Current Biology · doi:10.1016/j.cub.2019.05.009 · Cited by 63 · see citing works
Liao, G., Kinney, C. E., An, J. J., & Xu, B. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1815744116 · Cited by 65 · see citing works
Norris, A. J., Shaker, J. R., Cone, A. L., Ndiokho, I., & Bruchas, M. R. (2021) · eLife · doi:10.7554/elife.60779 · Cited by 61 · see citing works
Nakamura, Y., Yahiro, T., Fukushima, A., Kataoka, N., Hioki, H., & Nakamura, K. (2022) · Science Advances · doi:10.1126/sciadv.add5463 · Cited by 61 · see citing works
Cold-induced hyperphagia requires AgRP neuron activation in mice
Deem, J. D., Faber, C. L., Pedersen, C. E., Phan, B. A., Larsen, S. A., Ogimoto, K., Nelson, J. T., Damian, V. M., Tran, M. A., Palmiter, R. D., et al. (2020) · eLife · doi:10.7554/elife.58764 · Cited by 57 · see citing works
Cellular Composition of the Preoptic Area Regulating Sleep, Parental, and Sexual Behavior
Tsuneoka, Y., & Funato, H. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.649159 · Cited by 57 · see citing works
Zhou, Q., Fu, X., Xu, J., Dong, S., Liu, C., Cheng, D., Gao, C., Huang, M., Liu, Z., Ni, X., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.11.008 · Cited by 56 · see citing works
Sensory input, sex and function shape hypothalamic cell type development
Kaplan, H. S., Logeman, B. L., Zhang, K., Yawitz, T. A., Santiago, C., Sohail, N., Talay, M., Seo, C., Naumenko, S., Sui, S. J. H., et al. (2025) · Nature · doi:10.1038/s41586-025-08603-0 · Cited by 53 · see citing works
Impact of Adaptive Thermogenesis in Mice on the Treatment of Obesity
Bastías-Pérez, M., Zagmutt, S., Soler‐Vázquez, M. C., Serra, D., Mera, P., & Herrero, L. (2020) · Cells · doi:10.3390/cells9020316 · Cited by 52 · see citing works
Experience-dependent mechanisms in the regulation of parental care
Stolzenberg, D. S., & Mayer, H. S. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.04.002 · Cited by 52 · see citing works
Recovery of missing single-cell RNA-sequencing data with optimized transcriptomic references
Pool, A., Poldsam, H., Chen, S., Thomson, M. W., & Oka, Y. (2023) · Nature Methods · doi:10.1038/s41592-023-02003-w · Cited by 50 · see citing works
The neural circuits of thermal perception
Bokiniec, P., Zampieri, N., Lewin, G. R., & Poulet, J. F. A. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.04.006 · Cited by 52 · see citing works
Trivedi, A. K., Sur, S., Sharma, A., Taufique, S. K. T., Gupta, N., & Kumar, V. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.110454 · Cited by 52 · see citing works
Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins
Upton, B. A., Díaz, N. M., Gordon, S. A., Gelder, R. N. V., Buhr, E. D., & Lang, R. A. (2021) · Journal of Biological Rhythms · doi:10.1177/0748730421999870 · Cited by 52 · see citing works
Cellular populations and thermosensing mechanisms of the hypothalamic thermoregulatory center
Siemens, J., & Kamm, G. B. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-2101-0 · Cited by 50 · see citing works
A parabrachial-hypothalamic parallel circuit governs cold defense in mice
Yang, W. Z., Xie, H., Du, X., Zhou, Q., Xiao, Y., Zhao, Z., Jia, X., Xu, J., Zhang, W., Cai, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40504-6 · Cited by 54 · see citing works
Hypothalamic Kisspeptin Neurons and the Control of Homeostasis
Rønnekleiv, O. K., Qiu, J., & Kelly, M. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab253 · Cited by 48 · see citing works
The Hypothalamic Preoptic Area and Body Weight Control
Yu, S., François, M., Huesing, C., & Münzberg, H. (2017) · Neuroendocrinology · doi:10.1159/000479875 · Cited by 47 · see citing works
Recent advances in understanding the role of leptin in energy homeostasis
Münzberg, H., Singh, P., Heymsfield, S. B., Yu, S., & Morrison, C. D. (2020) · F1000Research · doi:10.12688/f1000research.24260.1 · Cited by 47 · see citing works
A forebrain neural substrate for behavioral thermoregulation
Jung, S., Lee, M., Kim, D., Son, C., Ahn, B. H., Heo, G., Park, J., Kim, M., Park, H., Koo, D.-J., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.09.039 · Cited by 49 · see citing works
Neurons in the Dorsomedial Hypothalamus Promote, Prolong, and Deepen Torpor in the Mouse
Ambler, M., Hitrec, T., Wilson, A., Cerri, M., & Pickering, A. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2102-21.2022 · Cited by 48 · see citing works
A Skin-Inspired Self-Adaptive System for Temperature Control During Dynamic Wound Healing
Geng, Y., Chen, G., Cao, R., Dai, H., Hu, Z., Yu, S., Wang, L., Zhu, L., Xiang, H., & Zhu, M. (2024) · Nano-Micro Letters · doi:10.1007/s40820-024-01345-0 · Cited by 48 · see citing works
Reactive and predictive homeostasis: Roles of orexin/hypocretin neurons
Burdakov, D. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.10.024 · Cited by 47 · see citing works
Efferent neural pathways for the control of brown adipose tissue thermogenesis and shivering
Morrison, S. F. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63912-7.00017-5 · Cited by 43 · see citing works
Reitz, S. L., Wasilczuk, A. Z., Beh, G. H., Proekt, A., & Kelz, M. B. (2020) · Current Biology · doi:10.1016/j.cub.2020.10.050 · Cited by 46 · see citing works
Cysteine depletion triggers adipose tissue thermogenesis and weight loss
Lee, A. H., Orliaguet, L., Youm, Y.-H., Maeda, R., Dlugos, T., Lei, Y., Coman, D., Shchukina, I., Andhey, P. S., Smith, S. R., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01297-8 · Cited by 45 · see citing works
Thermoregulatory inversion: a novel thermoregulatory paradigm
Tupone, D., Cano, G., & Morrison, S. F. (2017) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00022.2017 · Cited by 45 · see citing works
Feng, C., Wang, Y., Zha, X., Cao, H., Huang, S., Cao, D., Zhang, K., Xie, T., Xu, X., Liang, Z., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.05.002 · Cited by 45 · see citing works
Stefanov, B.-A., Teixeira, A. P., Mansouri, M., Bertschi, A., Krawczyk, K., Hamri, G. C.-E., Xue, S., & Fussenegger, M. (2021) · Advancement of science · doi:10.1002/advs.202101813 · Cited by 38 · see citing works
Krajewski-Hall, S. J., Miranda Dos Santos, F., McMullen, N. T., Blackmore, E. M., & Rance, N. E. (2019) · Endocrinology · doi:10.1210/en.2018-00934 · Cited by 42 · see citing works
Genetic identification of preoptic neurons that regulate body temperature in mice
Machado, N., & Saper, C. B. (2021) · Temperature · doi:10.1080/23328940.2021.1993734 · Cited by 42 · see citing works
Neural circuits of long-term thermoregulatory adaptations to cold temperatures and metabolic demands
Mota, C. M. D., & Madden, C. J. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00785-8 · Cited by 42 · see citing works
- Authors
- Tan, C. L., Cooke, E. K., Leib, D. E., Lin, Y.-C., Daly, G. E., Zimmerman, C. A., & Knight, Z. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Knight, Zachary A.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 167
- Issue
- 1
- Pages
- 47-59.e15
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5062957
- OpenAlex
- W2520969273
- Cited by
- 402
- References
- 58
- Citations by year
- 2026: 37 · 2025: 37 · 2024: 61 · 2023: 36 · 2022: 31 · 2021: 55 · 2020: 40 · 2019: 30 · 2018: 50 · 2017: 21 · 2016: 3 · 2012: 1
- FWCI
- 27.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1dp2dk109533-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2-DK109533, P30DK098722, R01DK106399)
- National Institute of Neurological Disorders and Stroke (R01NS094781)
- Topics
- Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Keywords
- warm-sensitive neurons, thermoregulation, preoptic hypothalamus, brain-derived neurotrophic factor, PACAP, heat sensing, hypothermia, thermogenesis
- MeSH terms
- Animals, Behavior, Animal, Body Temperature Regulation, Gene Expression Regulation, Hot Temperature, Neurons, RNA, Messenger, Ventromedial Hypothalamic Nucleus, Sequence Analysis, RNA, Brain-Derived Neurotrophic Factor, Ribosomal Protein S6, Microdissection, Pituitary Adenylate Cyclase-Activating Polypeptide, Mice, Optogenetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
