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
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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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.
The authors declare no competing financial interests.
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.
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).
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.
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.
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.
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.
A procedure that involves removing part of the vagus nerve.
Organisms that maintain their core body temperature at a stable temperature.
Having a normal level of body water at rest. This condition implies an absence of absolute or relative excess hydration or dehydration.
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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