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The neural basis of homeostatic and anticipatory thirst

Key Points

  • Thirst has a key role in the maintenance of body fluid homeostasis by driving water intake to compensate for losses incurred as a result of breathing, sweating and the production of urine

  • Thirst is associated with the activation of neurons in the anterior cingulate cortex and insular cortex; activation of these neurons might be induced via relay midline thalamic neurons

  • Two distinct types of thirst emerge under different circumstances: homeostatic thirst is evoked in response to an existing water deficit, whereas anticipatory thirst occurs before an impending deficit

  • Homeostatic thirst is induced in response to hypernatraemia, hyperosmolality and hypovolaemia, whereas anticipatory thirst occurs in response to food intake or hyperthermia or before sleep

  • Thirst is rapidly inhibited by oropharyngeal afferents in response to water intake; inputs from gastric distension sensors can also provide feedback signals that suppress thirst

Abstract

Water intake is one of the most basic physiological responses and is essential to sustain life. The perception of thirst has a critical role in controlling body fluid homeostasis and if neglected or dysregulated can lead to life-threatening pathologies. Clear evidence suggests that the perception of thirst occurs in higher-order centres, such as the anterior cingulate cortex (ACC) and insular cortex (IC), which receive information from midline thalamic relay nuclei. Multiple brain regions, notably circumventricular organs such as the organum vasculosum lamina terminalis (OVLT) and subfornical organ (SFO), monitor changes in blood osmolality, solute load and hormone circulation and are thought to orchestrate appropriate responses to maintain extracellular fluid near ideal set points by engaging the medial thalamic–ACC/IC network. Thirst has long been thought of as a negative homeostatic feedback response to increases in blood solute concentration or decreases in blood volume. However, emerging evidence suggests a clear role for thirst as a feedforward adaptive anticipatory response that precedes physiological challenges. These anticipatory responses are promoted by rises in core body temperature, food intake (prandial) and signals from the circadian clock. Feedforward signals are also important mediators of satiety, inhibiting thirst well before the physiological state is restored by fluid ingestion. In this Review, we discuss the importance of thirst for body fluid balance and outline our current understanding of the neural mechanisms that underlie the various types of homeostatic and anticipatory thirst.

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Figure 1: Feedback mechanisms to maintain body fluid balance.
Figure 2: Neural pathways that control thirst homeostasis.
Figure 3: Optogenetic manipulation of neuronal activity.
Figure 4: Neural pathways involved in the anticipatory stimulation of thirst during food intake and hyperthermia.
Figure 5: Circadian regulation of thirst.

References

  1. 1

    Morgan, R. M., Patterson, M. J. & Nimmo, M. A. Acute effects of dehydration on sweat composition in men during prolonged exercise in the heat. Acta Physiol. Scand. 182, 37–43 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    Effros, R. M. et al. Epithelial lining fluid solute concentrations in chronic obstructive lung disease patients and normal subjects. J. Appl. Physiol. 99, 1286–1292 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    Griese, M., Noss, J. & Schramel, P. Elemental and ion composition of exhaled air condensate in cystic fibrosis. J. Cyst. Fibros. 2, 136–142 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Bolt, E. E., Hagens, M., Willems, D. & Onwuteaka-Philipsen, B. D. Primary care patients hastening death by voluntarily stopping eating and drinking. Ann. Family Med. 13, 421–428 (2015).

    Article  Google Scholar 

  5. 5

    Arima, H., Azuma, Y., Morishita, Y. & Hagiwara, D. Central diabetes insipidus. Nagoya J. Med. Sci. 78, 349–358 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Cuesta, M., Hannon, M. J. & Thompson, C. J. Adipsic diabetes insipidus in adult patients. Pituitary 20, 372–380 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7

    Eisenberg, Y. & Frohman, L. A. Adipsic diabetes insipidus: a review. Endocr. Pract. 22, 76–83 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8

    Manning, S., Shaffie, R. & Arora, S. Case Report: Severe hypernatremia from psychogenic adipsia. F1000Res. 6, 34 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    Pereira, M. C., Vieira, M. M., Pereira, J. S. & Salgado, D. Adipsia in a diabetes insipidus patient. Case Rep. Oncol. 8, 385–388 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Koch, C. A. & Fulop, T. Clinical aspects of changes in water and sodium homeostasis in the elderly. Rev. Endocr. Metab. Disord. 18, 49–66 (2017).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11

    Fitzsimons, J. T. The physiology of thirst and sodium appetite. Monogr. Physiol. Soc. 35, 1–572 (1979).

    Google Scholar 

  12. 12

    Johnson, A. K. The sensory psychobiology of thirst and salt appetite. Med. Sci. Sports Exerc. 39, 1388–1400 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13

    McKinley, M. J. & Johnson, A. K. The physiological regulation of thirst and fluid intake. News Physiol. Sci. 19, 1–6 (2004).

    PubMed  PubMed Central  Google Scholar 

  14. 14

    Zimmerman, C. A., Leib, D. E. & Knight, Z. A. Neural circuits underlying thirst and fluid homeostasis. Nat. Rev. Neurosci. 18, 459–469 (2017). This paper reviews recent studies dissecting the neural circuits underlying thirst.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15

    Bourque, C. W. Central mechanisms of osmosensation and systemic osmoregulation. Nat. Rev. Neurosci. 9, 519–531 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16

    Verbalis, J. G. Disorders of body water homeostasis. Best Pract. Res. Clin. Endocrinol. Metab. 17, 471–503 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17

    Lafontan, M., Visscher, T. L., Farpour-Lambert, N. & Yumuk, V. Opportunities for intervention strategies for weight management: global actions on fluid intake patterns. Obes. Facts 8, 54–76 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18

    Popkin, B. M., D'Anci, K. E. & Rosenberg, I. H. Water, hydration, and health. Nutr. Rev. 68, 439–458 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19

    Orlandi, C., Zimmer, C. A. & Gheorghiade, M. Tolvaptan for the treatment of hyponatremia and congestive heart failure. Future Cardiol. 2, 627–634 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Redondo, N., Gomez-Martinez, S. & Marcos, A. Sensory attributes of soft drinks and their influence on consumers' preferences. Food Function 5, 1686–1694 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Adler, S. M. & Verbalis, J. G. Disorders of body water homeostasis in critical illness. Endocrinol. Metab. Clin. North Am. 35, 873–894 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Brvar, M. et al. Polydipsia as another mechanism of hyponatremia after 'ecstasy' (3,4 methyldioxymethamphetamine) ingestion. Eur. J. Emerg. Med. 11, 302–304 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23

    Kalantar-Zadeh, K., Nguyen, M. K., Chang, R. & Kurtz, I. Fatal hyponatremia in a young woman after ecstasy ingestion. Nat. Clin. Pract. Nephrol. 2, 283–288 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24

    Traub, S. J., Hoffman, R. S. & Nelson, L. S. The “ecstasy” hangover: hyponatremia due to 3,4-methylenedioxymethamphetamine. J. Urban Health 79, 549–555 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25

    Sandifer, M. G. Hyponatremia due to psychotropic drugs. J. Clin. Psychiatry 44, 301–303 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Lu, X. & Wang, X. Hyponatremia induced by antiepileptic drugs in patients with epilepsy. Expert Opin. Drug Safety 16, 77–87 (2017).

    CAS  Article  Google Scholar 

  27. 27

    Furth, S. & Oski, F. A. Hyponatremia and water intoxication. Am. J. Dis. Child. 147, 932–933 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Kushnir, M., Schattner, A., Ezri, T. & Konichezky, S. Schizophrenia and fatal self-induced water intoxication with appropriately-diluted urine. Am. J. Med. Sci. 300, 385–387 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29

    Patel, J. K. Polydipsia, hyponatremia, and water intoxication among psychiatric patients. Hospital Commun. Psychiatry 45, 1073–1074 (1994).

    CAS  Google Scholar 

  30. 30

    Ofran, Y., Lavi, D., Opher, D., Weiss, T. A. & Elinav, E. Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L−1): a disorder linked to female gender and psychiatric disorders. J. Intern. Med. 256, 525–528 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Turk, E. E., Schulz, F., Koops, E., Gehl, A. & Tsokos, M. Fatal hypernatremia after using salt as an emetic — report of three autopsy cases. Leg. Med. 7, 47–50 (2005).

    Article  CAS  Google Scholar 

  32. 32

    Kirkman, M. A., Albert, A. F., Ibrahim, A. & Doberenz, D. Hyponatremia and brain injury: historical and contemporary perspectives. Neurocrit. Care 18, 406–416 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33

    De Smet, H. R., Menadue, M. F., Oliver, J. R. & Phillips, P. A. Increased thirst and vasopressin secretion after myocardial infarction in rats. Am. J. Physiol. 285, R1203–R1211 (2003).

    CAS  Google Scholar 

  34. 34

    Sonneville, R. et al. Understanding brain dysfunction in sepsis. Ann. Intensive Care 3, 15 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35

    Lyons, O. D., Bradley, T. D. & Chan, C. T. Hypervolemia and sleep apnea in kidney disease. Semin. Nephrol. 35, 373–382 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36

    Iwasa, M. & Takei, Y. Pathophysiology and management of hepatic encephalopathy 2014 update: ammonia toxicity and hyponatremia. Hepatol. Res. 45, 1155–1162 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37

    Wier, L. M. et al. HCUP Facts and Figures: Statistics on Hospital-Based Care in the United States, 2009 (Agency for Healthcare and Research and Quality, 2011).

    Google Scholar 

  38. 38

    Magder, S. Volume and its relationship to cardiac output and venous return. Crit. Care 20, 271 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Moranville, M. P., Mieure, K. D. & Santayana, E. M. Evaluation and management of shock states: hypovolemic, distributive, and cardiogenic shock. J. Pharm. Pract. 24, 44–60 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Senay Jr., L. C. & Christensen, M. L. Changes in blood plasma during progressive dehydration. J. Appl. Physiol. 20, 1136–1140 (1965).

    Article  Google Scholar 

  41. 41

    Bedford, J. J. & Leader, J. P. Response of tissues of the rat to anisosmolality in vivo. Am. J. Physiol. 264, R1164–R1179 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Ayus, J. C., Varon, J. & Arieff, A. I. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann. Intern. Med. 132, 711–714 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43

    Machino, T. & Yoshizawa, T. Brain shrinkage due to acute hypernatremia. Neurology 67, 880 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44

    Spigset, O. & Hedenmalm, K. Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by psychotropic drugs. Drug Safety 12, 209–225 (1995).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45

    Sterns, R. H. Disorders of plasma sodium—causes, consequences, and correction. N. Engl. J. Med. 372, 55–65 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Stricker, E. M. & Sved, A. F. Thirst. Nutr. 16, 821–826 (2000).

    CAS  Article  Google Scholar 

  47. 47

    Rullier, S. Soif [French]. Dictionaire des Sciences Medicales 51, 448–490 (1821).

    Google Scholar 

  48. 48

    Cannon, W. B. Croonian Lecture: The physiological basis of thirst. Proc. R. Soc. Lond. B Biol. Sci. 90, 283–301 (1918).

    CAS  Article  Google Scholar 

  49. 49

    Wettendorff, H. Modifications de sang sous I'influence de la privation d'eau: contribution a l'étude de la soif [French]. Travaux du Laboratoire de Physiologie, Institut de Physiologie, Instituts, Solvay 4, 353–384. (1901).

    Google Scholar 

  50. 50

    Robinson, B. W. & Mishkin, M. Alimentary responses to forebrain stimulation in monkeys. Exp. Brain Res. 4, 330–366 (1968).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    Craig, A. D. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. 52

    Craig, A. D. A new view of pain as a homeostatic emotion. Trends Neurosci. 26, 303–307 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53

    Denton, D. A., McKinley, M. J., Farrell, M. & Egan, G. F. The role of primordial emotions in the evolutionary origin of consciousness. Conscious. Cogn. 18, 500–514 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54

    Denton, D. et al. Correlation of regional cerebral blood flow and change of plasma sodium concentration during genesis and satiation of thirst. Proc. Natl Acad. Sci. USA 96, 2532–2537 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55

    Denton, D. et al. Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness. Proc. Natl Acad. Sci. USA 96, 5304–5309 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56

    Farrell, M. J. et al. Unique, common, and interacting cortical correlates of thirst and pain. Proc. Natl Acad. Sci. USA 103, 2416–2421 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57

    Saker, P. et al. Regional brain responses associated with drinking water during thirst and after its satiation. Proc. Natl Acad. Sci. USA 111, 5379–5384 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58

    Farrell, M. J. et al. Cortical activation and lamina terminalis functional connectivity during thirst and drinking in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R623–R631 (2011). This human fMRI study reveals the brain regions involved in generating thirst.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59

    Egan, G. et al. Neural correlates of the emergence of consciousness of thirst. Proc. Natl Acad. Sci. USA 100, 15241–15246 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60

    Saker, P., Farrell, M. J., Egan, G. F., McKinley, M. J. & Denton, D. A. Overdrinking, swallowing inhibition, and regional brain responses prior to swallowing. Proc. Natl Acad. Sci. USA 113, 12274–12279 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Becker, C. A., Flaisch, T., Renner, B. & Schupp, H. T. From thirst to satiety: the anterior mid-cingulate cortex and right posterior insula indicate dynamic changes in incentive value. Front. Hum. Neurosci. 11, 234 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62

    Duncan, G. E. et al. Metabolic mapping of functional activity in rat brain and pituitary after water deprivation. Neuroendocrinology 49, 489–495 (1989).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63

    Pastuskovas, C. V., Cassell, M. D., Johnson, A. K. & Thunhorst, R. L. Increased cellular activity in rat insular cortex after water and salt ingestion induced by fluid depletion. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R1119–R1125 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64

    Craig, A. D. Interoception: the sense of the physiological condition of the body. Curr. Opin. Neurobiol. 13, 500–505 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65

    Hollis, J. H., McKinley, M. J., D'Souza, M., Kampe, J. & Oldfield, B. J. The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex; a neuroanatomical framework for the generation of thirst. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R1390–R1401 (2008). This anatomical study demonstrates brain regions and circuits involved in generating thirst in rats.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. 66

    McCormick, D. A. & Bal, T. Sensory gating mechanisms of the thalamus. Curr. Opin. Neurobiol. 4, 550–556 (1994).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67

    Andrews, W. H. & Orbach, J. Sodium receptors activating some nerves of perfused rabbit livers. Am. J. Physiol. 227, 1273–1275 (1974).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68

    Adachi, A. Thermosensitive and osmoreceptive afferent fibers in the hepatic branch of the vagus nerve. J. Auton. Nerv. Syst. 10, 269–273 (1984).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. 69

    Adachi, A., Niijima, A. & Jacobs, H. L. An hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioral studies. Am. J. Physiol. 231, 1043–1049 (1976).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70

    Andrews, W. H. & Orbach, J. Effect of osmotic pressure on spontaneous afferent discharge in the nerves of the perfused rabbit liver. Pflugers Arch. 361, 89–94 (1975).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71

    Choi-Kwon, S. & Baertschi, A. J. Splanchnic osmosensation and vasopressin: mechanisms and neural pathways. Am. J. Physiol. 261, E18–E25 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    King, M. S. & Baertschi, A. J. Central neural pathway mediating splanchnic osmosensation. Brain Res. 550, 268–278 (1991).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73

    Haberich, F. J. Osmoreception in the portal circulation. Fed. Proc. 27, 1137–1141 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Chwalbinska-Moneta, J. Role of hepatic portal osmoreception in the control of ADH release. Am. J. Physiol. 236, E603–E609 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Baertschi, A. J. & Vallet, P. G. Osmosensitivity of the hepatic portal vein area and vasopressin release in rats. J. Physiol. 315, 217–230 (1981).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  76. 76

    Andersson, B., Jobin, M. & Olsson, K. A study of thirst and other effects of an increased sodium concentration in the 3rd brain ventricle. Acta Physiol. Scand. 69, 29–36 (1967).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  77. 77

    McKinley, M. J., Blaine, E. H. & Denton, D. A. Brain osmoreceptors, cerebrospinal fluid electrolyte composition and thirst. Brain Res. 70, 532–537 (1974).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  78. 78

    McKinley, M. J., Denton, D. A. & Weisinger, R. S. Sensors for antidiuresis and thirst — osmoreceptors or CSF sodium detectors? Brain Res. 141, 89–103 (1978).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79

    Olsson, K. Further evidence for the importance of CSF Na+ concentration in central control of fluid balance. Acta Physiol. Scand. 88, 183–188 (1973).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  80. 80

    Olsson, K. Attenuation of dehydrative thirst by lowering of the CSF [Na+]. Acta Physiol. Scand. 94, 536–538 (1975).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  81. 81

    Weisinger, R. S., Considine, P., Denton, D. A. & McKinley, M. J. Rapid effect of change in cerebrospinal fluid sodium concentration on salt appetite. Nature 280, 490–491 (1979).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  82. 82

    Vivas, L., Chiaraviglio, E. & Carrer, H. F. Rat organum vasculosum laminae terminalis in vitro: responses to changes in sodium concentration. Brain Res. 519, 294–300 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  83. 83

    Voisin, D. L. & Bourque, C. W. Integration of sodium and osmosensory signals in vasopressin neurons. Trends Neurosci. 25, 199–205 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  84. 84

    Noda, M. & Hiyama, T. Y. Sodium sensing in the brain. Pflugers Arch. 467, 465–474 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. 85

    Voisin, D. L., Chakfe, Y. & Bourque, C. W. Coincident detection of CSF Na+ and osmotic pressure in osmoregulatory neurons of the supraoptic nucleus. Neuron 24, 453–460 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  86. 86

    Miller, R. L. & Loewy, A. D. ENaC γ-expressing astrocytes in the circumventricular organs, white matter, and ventral medullary surface: sites for Na+ regulation by glial cells. J. Chem. Neuroanat. 53, 72–80 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  87. 87

    Miller, R. L., Wang, M. H., Gray, P. A., Salkoff, L. B. & Loewy, A. D. ENaC-expressing neurons in the sensory circumventricular organs become c-Fos activated following systemic sodium changes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R1141–R1152 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88

    Ruiz, C., Gutknecht, S., Delay, E. & Kinnamon, S. Detection of NaCl and KCl in TRPV1 knockout mice. Chemical Senses 31, 813–820 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  89. 89

    Teruyama, R., Sakuraba, M., Wilson, L. L., Wandrey, N. E. & Armstrong, W. E. Epithelial Na+ sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei. Am. J. Physiol. Endocrinol. Metab. 302, E273–E285 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90

    Tanaka, M. et al. Molecular and functional remodeling of electrogenic membrane of hypothalamic neurons in response to changes in their input. Proc. Natl Acad. Sci. USA 96, 1088–1093 (1999).

    CAS  Article  Google Scholar 

  91. 91

    Hiyama, T. Y. et al. Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. Neuron 66, 508–522 (2010).

    CAS  Article  Google Scholar 

  92. 92

    Hiyama, T. Y., Watanabe, E., Okado, H. & Noda, M. The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior. J. Neurosci. 24, 9276–9281 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  93. 93

    Hiyama, T. Y. et al. Na(x) channel involved in CNS sodium-level sensing. Nat. Neurosci. 5, 511–512 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  94. 94

    Matsumoto, M. et al. Channel properties of Nax expressed in neurons. PLoS ONE 10, e0126109 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Goldin, A. L. Resurgence of sodium channel research. Annu. Rev. Physiol. 63, 871–894 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. 96

    Bourque, C. W., Voisin, D. L. & Chakfe, Y. Stretch-inactivated cation channels: cellular targets for modulation of osmosensitivity in supraoptic neurons. Progress Brain Res. 139, 85–94 (2002).

    CAS  Article  Google Scholar 

  97. 97

    Ciura, S. & Bourque, C. W. Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality. J. Neurosci. 26, 9069–9075 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  98. 98

    Bourque, C. W., Oliet, S. H. & Richard, D. Osmoreceptors, osmoreception, and osmoregulation. Front. Neuroendocrinol. 15, 231–274 (1994).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  99. 99

    Desson, S. E. & Ferguson, A. V. Interleukin 1beta modulates rat subfornical organ neurons as a result of activation of a non-selective cationic conductance. J. Physiol. 550, 113–122 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  100. 100

    Amin, M. S. et al. Distribution of epithelial sodium channels and mineralocorticoid receptors in cardiovascular regulatory centers in rat brain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R1787–R1797 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  101. 101

    Watanabe, E. et al. Nav2/NaG channel is involved in control of salt-intake behavior in the CNS. J. Neurosci. 20, 7743–7751 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  102. 102

    Coble, J. P., Grobe, J. L., Johnson, A. K. & Sigmund, C. D. Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308, R238–R249 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  103. 103

    Mimee, A., Smith, P. M. & Ferguson, A. V. Circumventricular organs: targets for integration of circulating fluid and energy balance signals? Physiol. Behav. 121, 96–102 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  104. 104

    Zimmerman, C. A. et al. Thirst neurons anticipate the homeostatic consequences of eating and drinking. Nature 537, 680–684 (2016). This study demonstrates that thirst-promoting SFO neurons are required for prandial thirst.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  105. 105

    Miselis, R. R., Shapiro, R. E. & Hand, P. J. Subfornical organ efferents to neural systems for control of body water. Science 205, 1022–1025 (1979).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  106. 106

    Nissen, R., Bourque, C. W. & Renaud, L. P. Membrane properties of organum vasculosum lamina terminalis neurons recorded in vitro. Am. J. Physiol. 264, R811–R815 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107

    Kinsman, B. J., Simmonds, S. S., Browning, K. N. & Stocker, S. D. Organum vasculosum of the lamina terminalis detects NaCl to elevate sympathetic nerve activity and blood pressure. Hypertension 69, 163–170 (2017).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  108. 108

    Sibbald, J. R., Hubbard, J. I. & Sirett, N. E. Responses from osmosensitive neurons of the rat subfornical organ in vitro. Brain Res. 461, 205–214 (1988).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  109. 109

    Grob, M., Drolet, G. & Mouginot, D. Specific Na+ sensors are functionally expressed in a neuronal population of the median preoptic nucleus of the rat. J. Neurosci. 24, 3974–3984 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. 110

    Tremblay, C. et al. Neuronal sodium leak channel is responsible for the detection of sodium in the rat median preoptic nucleus. J. Neurophysiol. 105, 650–660 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  111. 111

    Shimizu, H. et al. Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. Neuron 54, 59–72 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  112. 112

    Camacho, A. & Phillips, M. I. Horseradish peroxidase study in rat of the neural connections of the organum vasculosum of the lamina terminalis. Neurosci. Lett. 25, 201–204 (1981).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  113. 113

    Oka, Y., Ye, M. & Zuker, C. S. Thirst driving and suppressing signals encoded by distinct neural populations in the brain. Nature 520, 349–352 (2015). This study demonstrates that SFO neurons containing nitric oxide synthase (NOS) promote thirst.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  114. 114

    Gizowski, C., Zaelzer, C. & Bourque, C. W. Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep. Nature 537, 685–688 (2016). This study demonstrates that thirst prior to sleep is driven by the circadian clock.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  115. 115

    McKinley, M. J. et al. The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis. Acta Physiol. 214, 8–32 (2015).

    CAS  Article  Google Scholar 

  116. 116

    Saper, C. B. & Levisohn, D. Afferent connections of the median preoptic nucleus in the rat: anatomical evidence for a cardiovascular integrative mechanism in the anteroventral third ventricular (AV3V) region. Brain Res. 288, 21–31 (1983).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  117. 117

    Lind, R. W., Van Hoesen, G. W. & Johnson, A. K. An HRP study of the connections of the subfornical organ of the rat. J. Comp. Neurol. 210, 265–277 (1982).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  118. 118

    Nation, H. L., Nicoleau, M., Kinsman, B. J., Browning, K. N. & Stocker, S. D. DREADD-induced activation of subfornical organ neurons stimulates thirst and salt appetite. J. Neurophysiol. 115, 3123–3129 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  119. 119

    Abbott, S. B., Machado, N. L., Geerling, J. C. & Saper, C. B. Reciprocal control of drinking behavior by median preoptic neurons in mice. J. Neurosci. 36, 8228–8237 (2016). This study demonstrates that optogenetic activation of glutamatergic MnPO/OVLT neurons drives thirst.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  120. 120

    Allen, W. E. et al. Thirst-associated preoptic neurons encode an aversive motivational drive. Science 357, 1149–1155 (2017). This study demonstrates that MnPO neurons encode the negative valence associated with thirst.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  121. 121

    Gilman, A. The relation between blood osmotic pressure, fluid distribution and voluntary water intake. Am. J. Physiol. 120, 323–328 (1937).

    CAS  Article  Google Scholar 

  122. 122

    Wolf, A. V. Osmometric analysis of thirst in man and dog. Am. J. Physiol. 161, 75–86 (1950).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  123. 123

    Stricker, E. M. Osmoregulation and volume regulation in rats: inhibition of hypovolemic thirst by water. Am. J. Physiol. 217, 98–105 (1969).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  124. 124

    Anderson, J. W., Washburn, D. L. & Ferguson, A. V. Intrinsic osmosensitivity of subfornical organ neurons. Neuroscience 100, 539–547 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  125. 125

    Kucharczyk, J., Assaf, S. Y. & Mogenson, G. J. Differential effects of brain lesions on thirst induced by the administration of angiotensin-II to the preoptic region, subfornical organ and anterior third ventricle. Brain Res. 108, 327–337 (1976).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  126. 126

    Thrasher, T. N., Simpson, J. B. & Ramsay, D. J. Lesions of the subfornical organ block angiotensin-induced drinking in the dog. Neuroendocrinology 35, 68–72 (1982).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  127. 127

    Johnson, A. K. & Buggy, J. Periventricular preoptic-hypothalamus is vital for thirst and normal water economy. Am. J. Physiol. 234, R122–R129 (1978).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  128. 128

    Buggy, J. & Jonhson, A. K. Preoptic-hypothalamic periventricular lesions: thirst deficits and hypernatremia. Am. J. Physiol. 233, R44–R52 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129

    Thrasher, T. N., Keil, L. C. & Ramsay, D. J. Lesions of the organum vasculosum of the lamina terminalis (OVLT) attenuate osmotically-induced drinking and vasopressin secretion in the dog. Endocrinology 110, 1837–1839 (1982).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  130. 130

    Mangiapane, M. L., Thrasher, T. N., Keil, L. C., Simpson, J. B. & Ganong, W. F. Deficits in drinking and vasopressin secretion after lesions of the nucleus medianus. Neuroendocrinology 37, 73–77 (1983).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  131. 131

    Johnson, A. K., Cunningham, J. T. & Thunhorst, R. L. Integrative role of the lamina terminalis in the regulation of cardiovascular and body fluid homeostasis. Clin. Exp. Pharmacol. Physiol. 23, 183–191 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  132. 132

    McKinley, M. J. et al. Efferent neural pathways of the lamina terminalis subserving osmoregulation. Progress Brain Res. 91, 395–402 (1992).

    CAS  Article  Google Scholar 

  133. 133

    McKinley, M. J., Denton, D. A., Oldfield, B. J., De Oliveira, L. B. & Mathai, M. L. Water intake and the neural correlates of the consciousness of thirst. Semin. Nephrol. 26, 249–257 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  134. 134

    Ciura, S., Liedtke, W. & Bourque, C. W. Hypertonicity sensing in organum vasculosum lamina terminalis neurons: a mechanical process involving TRPV1 but not TRPV4. J. Neurosci. 31, 14669–14676 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  135. 135

    Zaelzer, C. et al. ΔN-TRPV1: a molecular co-detector of body temperature and osmotic stress. Cell Rep. 13, 23–30 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  136. 136

    Sharif-Naeini, R., Ciura, S., Zhang, Z. & Bourque, C. W. Contribution of TRPV channels to osmosensory transduction, thirst, and vasopressin release. Kidney Int. 73, 811–815 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  137. 137

    Sudbury, J. R., Ciura, S., Sharif-Naeini, R. & Bourque, C. W. Osmotic and thermal control of magnocellular neurosecretory neurons — role of an N-terminal variant of trpv1. Eur. J. Neurosci. 32, 2022–2030 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  138. 138

    Kinsman, B. et al. Osmoregulatory thirst in mice lacking the transient receptor potential vanilloid type 1 (TRPV1) and/or type 4 (TRPV4) receptor. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R1092–R1100 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  139. 139

    Taylor, A. C., McCarthy, J. J. & Stocker, S. D. Mice Lacking the transient receptor vanilloid potential 1 (TRPV1) channel display normal thirst responses and central Fos activation to hypernatremia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R1285–R1293 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  140. 140

    Hussy, N., Deleuze, C., Pantaloni, A., Desarmenien, M. G. & Moos, F. Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation. J. Physiol. 502, 609–621 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  141. 141

    Choe, K. Y., Olson, J. E. & Bourque, C. W. Taurine release by astrocytes modulates osmosensitive glycine receptor tone and excitability in the adult supraoptic nucleus. J. Neurosci. 32, 12518–12527 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  142. 142

    Choe, K. Y., Trudel, E. & Bourque, C. W. Effects of salt loading on the regulation of rat hypothalamic magnocellular neurosecretory cells by ionotropic GABA and glycine receptors. J Neuroendocrinol 28 (2016).

  143. 143

    Hussy, N., Deleuze, C., Desarmenien, M. G. & Moos, F. C. Osmotic regulation of neuronal activity: a new role for taurine and glial cells in a hypothalamic neuroendocrine structure. Prog. Neurobiol. 62, 113–134 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  144. 144

    Prager-Khoutorsky, M. & Bourque, C. W. Anatomical organization of the rat organum vasculosum laminae terminalis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309, R324–R337 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  145. 145

    Hochstenbach, S. L. & Ciriello, J. Effect of lesions of forebrain circumventricular organs on c-fos expression in the central nervous system to plasma hypernatremia. Brain Res. 713, 17–28 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  146. 146

    Lechner, S. G. et al. The molecular and cellular identity of peripheral osmoreceptors. Neuron 69, 332–344 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  147. 147

    Russell, P. J., Abdelaal, A. E. & Mogenson, G. J. Graded levels of hemorrhage, thirst and angiotensin II in the rat. Physiol. Behav. 15, 117–119 (1975).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  148. 148

    Fitzsimons, J. T. Drinking by rats depleted of body fluid without increase in osmotic pressure. J. Physiol. 159, 297–309 (1961).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  149. 149

    Joris, L., Dab, I. & Quinton, P. M. Elemental composition of human airway surface fluid in healthy and diseased airways. Am. Rev. Respir. Dis. 148, 1633–1637 (1993).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  150. 150

    Zardetto-Smith, A. M., Thunhorst, R. L., Cicha, M. Z. & Johnson, A. K. Afferent signaling and forebrain mechanisms in the behavioral control of extracellular fluid volume. Ann. NY Acad. Sci. 689, 161–176 (1993).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  151. 151

    Fitzsimons, J. T. Angiotensin, thirst, and sodium appetite. Physiol Rev. 78, 583–686 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  152. 152

    Stocker, S. D., Stricker, E. M. & Sved, A. F. Arterial baroreceptors mediate the inhibitory effect of acute increases in arterial blood pressure on thirst. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282, R1718–R1729 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  153. 153

    Stocker, S. D., Stricker, E. M. & Sved, A. F. Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R214–R224 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  154. 154

    Stricker, E. M. & Sved, A. F. Controls of vasopressin secretion and thirst: similarities and dissimilarities in signals. Physiol. Behav. 77, 731–736 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  155. 155

    Dampney, R. A., Polson, J. W., Potts, P. D., Hirooka, Y. & Horiuchi, J. Functional organization of brain pathways subserving the baroreceptor reflex: studies in conscious animals using immediate early gene expression. Cell. Mol. Neurobiol. 23, 597–616 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  156. 156

    Thunhorst, R. L., Xu, Z., Cicha, M. Z., Zardetto-Smith, A. M. & Johnson, A. K. Fos expression in rat brain during depletion-induced thirst and salt appetite. Am. J. Physiol. 274, R1807–R1814 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Badoer, E., McKinley, M. J., Oldfield, B. J. & McAllen, R. M. Distribution of hypothalamic, medullary and lamina terminalis neurons expressing Fos after hemorrhage in conscious rats. Brain Res. 582, 323–328 (1992).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  158. 158

    Potts, P. D., Ludbrook, J., Gillman-Gaspari, T. A., Horiuchi, J. & Dampney, R. A. Activation of brain neurons following central hypervolaemia and hypovolaemia: contribution of baroreceptor and non-baroreceptor inputs. Neuroscience 95, 499–511 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  159. 159

    Godino, A., Giusti-Paiva, A., Antunes-Rodrigues, J. & Vivas, L. Neurochemical brain groups activated after an isotonic blood volume expansion in rats. Neuroscience 133, 493–505 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  160. 160

    Howe, B. M., Bruno, S. B., Higgs, K. A., Stigers, R. L. & Cunningham, J. T. FosB expression in the central nervous system following isotonic volume expansion in unanesthetized rats. Exp. Neurol. 187, 190–198 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  161. 161

    Randolph, R. R., Li, Q., Curtis, K. S., Sullivan, M. J. & Cunningham, J. T. Fos expression following isotonic volume expansion of the unanesthetized male rat. Am. J. Physiol. 274, R1345–R1352 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. 162

    Gizowski, C. & Bourque, C. W. Neurons that drive and quench thirst. Science 357, 1092–1093 (2017).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  163. 163

    Simpson, J. B. & Routtenberg, A. Subfornical organ: a dipsogenic site of action of angiotensin II. Science 201, 379–381 (1978).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  164. 164

    Simpson, J. B. & Routtenberg, A. Subfornical organ: site of drinking elicitation by angiotensin II. Science 181, 1172–1175 (1973).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  165. 165

    Antunes-Rodrigues, J., de Castro, M., Elias, L. L., Valenca, M. M. & McCann, S. M. Neuroendocrine control of body fluid metabolism. Physiol. Rev. 84, 169–208 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  166. 166

    Kuwahara, K. & Nakao, K. Regulation and significance of atrial and brain natriuretic peptides as cardiac hormones. Endocr. J. 57, 555–565 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  167. 167

    Ehrlich, K. J. & Fitts, D. A. Atrial natriuretic peptide in the subfornical organ reduces drinking induced by angiotensin or in response to water deprivation. Behav. Neurosci. 104, 365–372 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  168. 168

    Stanhewicz, A. E. & Kenney, W. L. Determinants of water and sodium intake and output. Nutr. Rev. 73 (Suppl. 2), 73–82 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  169. 169

    Stricker, E. M. & Stricker, M. L. Pre-systemic controls of fluid intake and vasopressin secretion. Physiol. Behav. 103, 86–88 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  170. 170

    Fitzsimons, T. J. & Le Magnen, J. Eating as a regulatory control of drinking in the rat. J. Comp. Physiol. Psychol. 67, 273–283 (1969).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  171. 171

    Mandelblat-Cerf, Y. et al. Bidirectional anticipation of future osmotic challenges by vasopressin neurons. Neuron 93, 57–65 (2017).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  172. 172

    Hatton, G. I. & Almli, C. R. Plasma osmotic pressure and volume changes as determinants of drinking thresholds. Physiol. Behav. 4, 207–214 (1969).

    Article  Google Scholar 

  173. 173

    Gamble, J. L., Putnam, M. C. & McKhann, C. F. The optimal water requirement in renal functions: 1. Measurements of water drinking by rats according to increments of urea and of several salts in the food. Am. J. Physiol. 88, 571–580 (1929).

    CAS  Article  Google Scholar 

  174. 174

    Kraly, F. S., Kim, Y. M., Dunham, L. M. & Tribuzio, R. A. Drinking after intragastric NaCl without increase in systemic plasma osmolality in rats. Am. J. Physiol. 269, R1085–R1092 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. 175

    Stricker, E. M., Huang, W. & Sved, A. F. Early osmoregulatory signals in the control of water intake and neurohypophyseal hormone secretion. Physiol. Behav. 76, 415–421 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  176. 176

    Manesh, R., Hoffmann, M. L. & Stricker, E. M. Water ingestion by rats fed a high-salt diet may be mediated, in part, by visceral osmoreceptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1742–R1749 (2006).

    CAS  Article  Google Scholar 

  177. 177

    Krause, E. G., de Kloet, A. D. & Sakai, R. R. Post-ingestive signals and satiation of water and sodium intake of male rats. Physiol. Behav. 99, 657–662 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  178. 178

    Kobashi, M. & Adachi, A. Projection of nucleus tractus solitarius units influenced by hepatoportal afferent signal to parabrachial nucleus. J. Autonom. Nerv. System 16, 153–158 (1986).

    CAS  Article  Google Scholar 

  179. 179

    Kobashi, M. & Adachi, A. Convergence of hepatic osmoreceptive inputs on sodium-responsive units within the nucleus of the solitary tract of the rat. J. Neurophysiol. 54, 212–219 (1985).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  180. 180

    Stricker, E. M. & Hoffmann, M. L. Presystemic signals in the control of thirst, salt appetite, and vasopressin secretion. Physiol. Behav. 91, 404–412 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  181. 181

    Morita, H. et al. Fos induction in rat brain neurons after stimulation of the hepatoportal Na-sensitive mechanism. Am. J. Physiol. 272, R913–923 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. 182

    Starbuck, E. M. & Fitts, D. A. Influence of the subfornical organ on meal-associated drinking in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R669–R677 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  183. 183

    Gu, G. B. & Ju, G. The parabrachio-subfornical organ projection in the rat. Brain Res. Bull. 38, 41–47 (1995).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  184. 184

    Han, Z. S., Gu, G. B., Sun, C. Q. & Ju, G. Convergence of somatosensory and baroreceptive inputs onto parabrachio-subfornical organ neurons in the rat: an electrophysiological study. Brain Res. 566, 239–247 (1991).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  185. 185

    McKinley, M. J. et al. The sensory circumventricular organs of the mammalian brain. Adv. Anat. Embryol. Cell Biol. 172, III–XII (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. 186

    Sladek, C. D. & Johnson, A. K. Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R669–R678 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  187. 187

    Bel'skaya, L. V., Kosenok, V. K. & Sarf, E. A. Chronophysiological features of the normal mineral composition of human saliva. Arch. Oral Biol. 82, 286–292 (2017).

    CAS  Article  Google Scholar 

  188. 188

    Lund, J. P., Barker, J. H., Dellow, P. G. & Stevenson, J. A. Water intake of normal and desalivate rats on exposure to environmental heat. Can. J. Physiol. Pharmacol. 47, 849–852 (1969).

    CAS  Article  Google Scholar 

  189. 189

    Grace, J. E. & Stevenson, J. A. Thermogenic drinking in the rat. Am. J. Physiol. 220, 1009–1015 (1971).

    CAS  Article  Google Scholar 

  190. 190

    Box, B. M., Montis, F., Yeomans, C. & Stevenson, J. A. Thermogenic drinking in cold-acclimated rats. Am. J. Physiol. 225, 162–165 (1973).

    CAS  Article  Google Scholar 

  191. 191

    Barney, C. C. & Folkerts, M. M. Thermal dehydration-induced thirst in rats: role of body temperature. Am. J. Physiol. 269, R557–R564 (1995).

    CAS  PubMed  Google Scholar 

  192. 192

    Morrison, S. F. & Nakamura, K. Central neural pathways for thermoregulation. Front. Biosci. 16, 74–104 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  193. 193

    Palkar, R., Lippoldt, E. K. & McKemy, D. D. The molecular and cellular basis of thermosensation in mammals. Curr. Opin. Neurobiol. 34, 14–19 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  194. 194

    Schepers, R. J. & Ringkamp, M. Thermoreceptors and thermosensitive afferents. Neurosci. Biobehav. Rev. 34, 177–184 (2010).

    CAS  Article  Google Scholar 

  195. 195

    Craig, A. D., Bushnell, M. C., Zhang, E. T. & Blomqvist, A. A thalamic nucleus specific for pain and temperature sensation. Nature 372, 770–773 (1994).

    CAS  Article  Google Scholar 

  196. 196

    Nakamura, K. & Morrison, S. F. A thermosensory pathway that controls body temperature. Nat. Neurosci. 11, 62–71 (2008).

    CAS  Article  Google Scholar 

  197. 197

    Jessen, C., Feistkorn, G. & Nagel, A. Temperature sensitivity of skeletal muscle in the conscious goat. J. Appl. Physiol. 54, 880–886 (1983).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  198. 198

    Fajardo, O., Meseguer, V., Belmonte, C. & Viana, F. TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: pharmacological and genetic evidence. J. Neurosci. 28, 7863–7875 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  199. 199

    Riedel, W. Warm receptors in the dorsal abdominal wall of the rabbit. Pflugers Arch. 361, 205–206 (1976).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  200. 200

    Rawson, R. O. & Quick, K. P. Localization of intra-abdominal thermoreceptors in the ewe. J. Physiol. 222, 665–667 (1972).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  201. 201

    Adelson, D. W., Wei, J. Y. & Kruger, L. Warm-sensitive afferent splanchnic C-fiber units in vitro. J. Neurophysiol. 77, 2989–3002 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  202. 202

    Wit, A. & Wang, S. C. Temperature-sensitive neurons in preoptic-anterior hypothalamic region: effects of increasing ambient temperature. Am. J. Physiol. 215, 1151–1159 (1968).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  203. 203

    Takamata, A., Mack, G. W., Stachenfeld, N. S. & Nadel, E. R. Body temperature modification of osmotically induced vasopressin secretion and thirst in humans. Am. J. Physiol. 269, R874–880 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  204. 204

    Boulant, J. A. Cellular mechanisms of temperature sensitivity in hypothalamic neurons. Progress Brain Res. 115, 3–8 (1998).

    CAS  Article  Google Scholar 

  205. 205

    Fealey, R. D. Interoception and autonomic nervous system reflexes thermoregulation. Handb. Clin. Neurol. 117, 79–88 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  206. 206

    Morrison, S. F. Central control of body temperature. F1000Res. 5, 880 (2016).

    Article  CAS  Google Scholar 

  207. 207

    Boulant, J. A. Hypothalamic mechanisms in thermoregulation. Fed. Proc. 40, 2843–2850 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. 208

    Barbour, H. G. Die wirkung unmittelbarer erwarmung und abkuhlung der warmezentra auf die korpertemperatur [German]. Arch. Exp. Path. Pharmak. 70, 1–15 (1912).

    Article  Google Scholar 

  209. 209

    Hammouda, M. The central and the reflex mechanism of panting. J. Physiol. 77, 319–336 (1933).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  210. 210

    Magoun, H. W., Harrison, F., Brobeck J. R., Ranson, S. W. & Paolini, P. Activation of heat loss mechanisms by local heating of the brain. J. Neurophysiol. 87, 885–905 (1986).

    Google Scholar 

  211. 211

    Jacobson, F. H. & Squires, R. D. Thermoregulatory responses of the cat to preoptic and environmental temperatures. Am. J. Physiol. 218, 1575–1582 (1970).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  212. 212

    Szczepanska-Sadowska, E. Plasma ADH increase and thirst suppression elicited by preoptic heating in the dog. Am. J. Physiol. 226, 155–161 (1974).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  213. 213

    Morrison, S. F., Nakamura, K. & Madden, C. J. Central control of thermogenesis in mammals. Exp. Physiol. 93, 773–797 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  214. 214

    Tan, C. L. et al. Warm-sensitive neurons that control body temperature. Cell 167, 47–59.e15 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  215. 215

    Nakamura, K. & Morrison, S. F. A thermosensory pathway mediating heat-defense responses. Proc. Natl Acad. Sci. USA 107, 8848–8853 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  216. 216

    Andersson, B. & Larsson, B. Influence of local temperature changes in the preoptic area and rostral hypothalamus on the regulation of food and water intake. Acta Physiol. Scand. 52, 75–89 (1961).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  217. 217

    Trudel, E. & Bourque, C. W. Circadian modulation of osmoregulated firing in rat supraoptic nucleus neurones. J. Neuroendocrinol. 24, 577–586 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  218. 218

    Moon, D. G. et al. Antidiuretic hormone in elderly male patients with severe nocturia: a circadian study. BJU Int. 94, 571–575 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  219. 219

    Miller, M. Nocturnal polyuria in older people: pathophysiology and clinical implications. J. Am. Geriatr. Soc. 48, 1321–1329 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  220. 220

    Tokonami, N. et al. Local renal circadian clocks control fluid-electrolyte homeostasis and BP. J. Am. Soc. Nephrol. 25, 1430–1439 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  221. 221

    Firsov, D., Tokonami, N. & Bonny, O. Role of the renal circadian timing system in maintaining water and electrolytes homeostasis. Mol. Cell. Endocrinol. 349, 51–55 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  222. 222

    Asplund, R. Nocturia, nocturnal polyuria, and sleep quality in the elderly. J. Psychosom. Res. 56, 517–525 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  223. 223

    Windle, R. J., Forsling, M. L. & Guzek, J. W. Daily rhythms in the hormone content of the neurohypophysial system and release of oxytocin and vasopressin in the male rat: effect of constant light. J. Endocrinol. 133, 283–290 (1992).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  224. 224

    Trudel, E. & Bourque, C. W. Central clock excites vasopressin neurons by waking osmosensory afferents during late sleep. Nat. Neurosci. 13, 467–474 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  225. 225

    Spiteri, N. J. Circadian patterning of feeding, drinking and activity during diurnal food access in rats. Physiol. Behav. 28, 139–147 (1982).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  226. 226

    Satinoff, E. & Prosser, R. A. Suprachiasmatic nuclear lesions eliminate circadian rhythms of drinking and activity, but not of body temperature, in male rats. J. Biol. Rhythms 3, 1–22 (1988).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  227. 227

    Johnson, R. F., Beltz, T. G., Thunhorst, R. L. & Johnson, A. K. Investigations on the physiological controls of water and saline intake in C57BL/6 mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285, R394–R403 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  228. 228

    Lee, J. E. et al. Endogenous peptide discovery of the rat circadian clock: a focused study of the suprachiasmatic nucleus by ultrahigh performance tandem mass spectrometry. Mol. Cell. Proteom. 9, 285–297 (2010).

    CAS  Google Scholar 

  229. 229

    Abrahamson, E. E. & Moore, R. Y. Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res. 916, 172–191 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  230. 230

    Kalsbeek, A. & Buijs, R. M. Output pathways of the mammalian suprachiasmatic nucleus: coding circadian time by transmitter selection and specific targeting. Cell Tissue Res. 309, 109–118 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  231. 231

    Moore, R. Y., Speh, J. C. & Leak, R. K. Suprachiasmatic nucleus organization. Cell Tissue Res. 309, 89–98 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  232. 232

    Appelgren, B., Eriksson, S. & Jonasson, H. Oro-gastro-intestinal inhibition of hypernatremia-induced drinking in the goat. Acta Physiol. Scand. 115, 273–280 (1982).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  233. 233

    Wood, R. J., Rolls, E. T. & Rolls, B. J. Physiological mechanisms for thirst in the nonhuman primate. Am. J. Physiol. 242, R423–R428 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  234. 234

    Krashes, M. J. Physiology: Forecast for water balance. Nature 537, 626–627 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  235. 235

    Zocchi, D., Wennemuth, G. & Oka, Y. The cellular mechanism for water detection in the mammalian taste system. Nat. Neurosci. 20, 927–933 (2017).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  236. 236

    Blass, E. M., Jobaris, R. & Hall, W. G. Oropharyngeal control of drinking in rats. J. Comp. Physiol. Psychol. 90, 909–916 (1976).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  237. 237

    Maddison, S., Wood, R. J., Rolls, E. T., Rolls, B. J. & Gibbs, J. Drinking in the rhesus monkey: peripheral factors. J. Comp. Physiol. Psychol. 94, 365–374 (1980).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  238. 238

    Davis, J. D., Smith, G. P. & McCann, D. P. The control of water and sodium chloride intake by postingestional and orosensory stimulation in water-deprived rats. Physiol. Behav. 75, 7–14 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  239. 239

    Paintal, A. S. Impulses in vagal afferent fibres from stretch receptors in the stomach and their role in the peripheral mechanism of hunger. Nature 172, 1194–1195 (1953).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  240. 240

    Malbert, C. H. & Leitner, L. M. Mechanoreceptors sensitive to flow at the gastroduodenal junction of the cat. Am. J. Physiol. 265, G310–G313 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. 241

    Paintal, A. S. A study of gastric stretch receptors; their role in the peripheral mechanism of satiation of hunger and thirst. J. Physiol. 126, 255–270 (1954).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  242. 242

    Raybould, H. E., Gayton, R. J. & Dockray, G. J. CNS effects of circulating CCK8: involvement of brainstem neurones responding to gastric distension. Brain Res. 342, 187–190 (1985).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  243. 243

    Olson, B. R. et al. c-Fos expression in rat brain and brainstem nuclei in response to treatments that alter food intake and gastric motility. Mol. Cell. Neurosci. 4, 93–106 (1993).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  244. 244

    Hyde, T. M. & Miselis, R. R. Area postrema and adjacent nucleus of the solitary tract in water and sodium balance. Am. J. Physiol. 247, R173–R182 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  245. 245

    Curtis, K. S., Verbalis, J. G. & Stricker, E. M. Area postrema lesions in rats appear to disrupt rapid feedback inhibition of fluid intake. Brain Res. 726, 31–38 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  246. 246

    Curtis, K. S. & Stricker, E. M. Enhanced fluid intake by rats after capsaicin treatment. Am. J. Physiol. 272, R704–R709 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  247. 247

    Hajat, S., Vardoulakis, S., Heaviside, C. & Eggen, B. Climate change effects on human health: projections of temperature-related mortality for the UK during the 2020s, 2050s and 2080s. J. Epidemiol. Commun. Health 68, 641–648 (2014).

    Article  Google Scholar 

  248. 248

    Robertson, G. L., Shelton, R. L. & Athar, S. The osmoregulation of vasopressin. Kidney Int. 10, 25–37 (1976).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors' work is supported by a Foundation Grant from the Canadian Institutes of Health Research (CIHR, FDN 143337), an operating grant from the Heart and Stroke Foundation of Canada (G-16-00014197), a James McGill Chair to C.W.B., and a Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award to C.G. The Research Institute of the McGill University Health Centre receives generous funding from the Fonds de Recherche Québec Santé.

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Both authors researched the data for the article, discussed its content and contributed to writing and editing the manuscript before submission.

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Correspondence to Charles W. Bourque.

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PowerPoint slides

Glossary

Adipsia

Lack of thirst even under conditions that normally stimulate thirst, such as dehydration.

Vasomotor tone

The degree of tension in the smooth muscles that surround blood vessels.

Tonicity

A measure of a solution's potential to attract or repel water across a semipermeable membrane and thus generate osmotic pressure. Solutions with a higher total concentration of solutes will attract water and vice versa.

Anterior cingulate cortex

ACC. The anterior part of the cingulate cortex, which is a midline structure that lies dorsal to the corpus callosum. The ACC has a role in regulating body homeostasis and higher-order functions such as reward anticipation and decision making.

Affective motivation

Motivation to complete a task driven by a particular emotion.

Primordial emotions

Instinctive processes that drive behaviour to maintain optimal body homeostasis (for example, thirst, hunger and pain).

Insular cortex

(IC). The portion of the cerebral cortex within the lateral sulcus. It is believed to have roles in consciousness, emotions and regulating body homeostasis.

Interoceptive sensory modalities

Sensory signals related to the internal state of the body and viscera (for example, stomach distension, temperature and acidity).

Cortex

The outermost portion of the brain, thought to mediate consciousness, memory, attention, awareness, language and thought.

Prefrontal regions

The anterior portions of the brain.

Autoradiographic metabolic trapping

A method of visualizing glucose utilization in the brain. It is used as a surrogate to indicate that neurons have been electrically activated.

Immediate early gene c-Fos

A gene that is transcribed and translated transiently and rapidly in response to increased cellular calcium. Expression of an immediate early gene often indicates that neurons have been electrically activated.

Somatosensory information

Signals that encode information relating to sensory modalities such as hearing, touch and vision.

Action potentials

All-or-none electrical impulses generated at the soma of a neuron. An action potential is rapidly conducted to the axon terminal, where it can activate voltage-gated calcium channels and stimulate transmitter release onto a distinct target neuron.

Membrane potential

The electrical potential of a cell.

Organum vasculosum lamina terminalis

(OVLT). A midline brain structure located in the ventral part of the lamina terminalis and contained within the preoptic area of the hypothalamus.

Subfornical organ

(SFO). A midline brain structure that is located at the dorsal aspect of the lamina terminalis and attached to the hippocampal commissure.

Circumventricular organs

Regions of the brain that lack a blood–brain barrier, such as the organum vasculosum lamina terminalis, subfornical organ and area postrema. Neurons in these regions are directly exposed to circulating substances in the blood.

Depolarized

A term used to designate that the membrane potential of a cell has become relatively more positive. In neurons, depolarization commonly causes an increase in electrical excitability.

Median preoptic nucleus

(MnPO). A midline region of the hypothalamus that is part of the lamina terminalis and lies directly above the organum vasculosum lamina terminalis. The MnPO is thought to be an integrative nucleus involved in regulating blood pressure, fluid balance and body temperature.

Optogenetic

A technique that uses light to activate a rhodopsin channel for the purpose of causing depolarization or hyperpolarization. The rhodopsin expression is directed by genetic approaches that enable the control of specific subsets of neurons.

Chemogenetic

A technique that uses a modified G-protein receptor that is specifically activated by a unique and otherwise biologically inactive drug. Because receptor expression can be targeted to specific cells, the drug can be used to control the activity of specific subsets of neurons.

Third ventricle

One of four interconnected cavities in the brain that are filled with cerebrospinal fluid. It is a midline ventricle surrounded by the hypothalamus and thalamus.

Fibre photometry

A technique used to detect changes in fluorescence in vivo by use of an implanted fibre-optic microprobe. When targeted to neurons expressing a calcium-sensitive fluorophore, the technique can be used as a surrogate indicator of neuronal activity.

Supraoptic nucleus

(SON). A nucleus within the hypothalamus that contains magnocellular neurosecretory cells. These cells project to the posterior pituitary (neurohypophysis) and release vasopressin and oxytocin into the circulating peripheral blood.

Vagotomy

A procedure that involves removing part of the vagus nerve.

Homeotherms

Organisms that maintain their core body temperature at a stable temperature.

Euhydrated

Having a normal level of body water at rest. This condition implies an absence of absolute or relative excess hydration or dehydration.

Neurohypophysis

The posterior part of the pituitary gland that contains axon terminals originating from magnocellular neurosecretory neurons in the supraoptic nucleus and paraventricular nucleus.

Magnocellular neurosecretory neurons

Neuroendocrine neurons that synthesize either vasopressin or oxytocin within the supraoptic nucleus and paraventricular nucleus.

Active period

The last 2 h of the wake period. Animals ingest significantly more water at this time compared to the basal period.

Basal period

The 2 h period preceding the active period. During the basal period, animals ingest small volumes of water.

Whole-cell currents

Electrical currents generated by the entire cell membrane and recorded by patch clamp electrophysiology.

Negative valence

Aversive or unpleasant emotion associated with an event or condition.

Oropharyngeal afferents

Nerve fibres carrying sensory signals that originate from different tissues in the mouth or pharynx.

Trigeminal nerve

The fifth cranial nerve; it is a sensory and motor nerve that transmits information responsible for much of orofacial sensation and mediates motor functions associated with biting and chewing.

Area postrema

(AP). A midline circumventricular organ in the brain stem that is involved in the detection of circulating substances, the relay of autonomic signals and the control of emesis.

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Gizowski, C., Bourque, C. The neural basis of homeostatic and anticipatory thirst. Nat Rev Nephrol 14, 11–25 (2018). https://doi.org/10.1038/nrneph.2017.149

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