ESPE Yearbook of Paediatric Endocrinology

Nature 2020 Dec; 588(7836): 112–117https://go.nature.com/3go7UjO

Thirst is sensed by two distinct types of stimuli – osmotic and hypovolaemic. The authors show that in mice these two stimuli act via separate mechanisms and neuron types, and lead to distinct drinking behavioural responses. High blood osmolality induces osmotic thirst that drives water consumption. By contrast, hypovolaemia drives intake of both water and salt-containing solutions.

The authors induced acute osmotic stress in mice by intraperitoneal injection of hypertonic solutes – this stimulus triggered selective consumption of H2O over NaCl solution. Alternatively, they induced acute hypovolaemia by administration of polyethylene glycol or furosemide – this increased intake of both H2O and NaCl solution.

They then used a ‘stimulus-to-cell-type mapping’ optogenetics approach together with single-cell RNA sequencing to identify the cellular substrates that underlie these distinct types of thirst. Circumventricular organs (CVO) in the lamina terminalis, part of the brain that lacks a blood–brain barrier, are critical sites for sensing both types of thirst-inducing stimuli. However, within these CVOs are separate neuron subpopulations, characterised by distinct single cell transcriptomic profiles, which are activated by either osmotic or hypovolaemic stimuli. In turn, these act via separate downstream brain targets to achieve one or the other behavioural response.

So, we have two types of thirst, but only one word for the two related but different sensations. Fortunately, our bodies know this and make us reach for either water or a sports drink.