The different thirst neurons (and why we sometimes prefer water over Gatorade)

Do you remember the last time you craved water? And that refreshing feeling when you finally were able to drink some? Perhaps it was after a long, sweaty run in the sun, or maybe it was after eating a bag of salty chips. But how does your brain know to tell you to drink water because your body lost fluid or had too much salt? While it was already known that several brain regions are responsible for thirst, Pool et al. set out to discover more specifically how these areas respond to different thirst stimuli.

When you have too much salt, you crave water, a concept called osmotic thirst. However, when you are thirsty after sweating a lot, you crave both salts and water (such as Gatorade and other electrolyte drinks), a concept called hypovolemic thirst. Natural dehydration is a combination of the two. Pool et al. hypothesized that there are different neuronal populations that respond to each type of thirst in the two main thirst areas of the brain, the subfornical organ (SFO) and the organum vasculosum lamina terminalis (OVLT).

They first grouped all the neurons in the SFO and OVLT of a control group of mice using a technique called single-cell RNA sequencing, which looks at the gene expression of each cell. Then, they repeated this protocol with four different groups of mice: mice that had free access to water, mice that were put under osmotic stress, mice that were put under hypovolemic stress, and mice that were water deprived. This time, they looked at which groups of neurons were differentially activated under each condition based on their gene expression profiles. They found at least one neuron group that was selectively activated by each type of thirst in the SFO and OVLT, as well as ones that were activated under both osmotic and hypovolemic stress. The water deprived mice, as predicted, activated cells of both types.

Using correlative analyses, they determined that the neurons that responded to osmotic thirst  expressed the Rxfp1 gene, and the neurons that responded to hypovolemic thirst expressed the Pdyn gene. They activated these neuronal populations in the SFO or OVLT using optogenetics - a method that uses light to turn neurons that express a light-responsive gene on or off. Indeed, activation of the neurons that expressed Rxfp1 induced a preference for drinking water in the mice. Activation of the neurons that expressed Pdyn caused the mice to drink both pure water and salt water. A graphical depiction of their findings is shown in the following figure.

Figure 1. Depending on whether the mouse is experiencing osmotic or hypovolemic thirst, different populations of neurons are activated leading to craving of either pure water or water with salts.  

The authors successfully confirmed the presence of distinct neuronal populations in the SFO and OVLT that respond to osmotic thirst, hypovolemic thirst, or both. However, their findings pose many questions that warrant further investigation. Are these Rxfp1 and Pdyn neuronal populations the sole drivers for the responses to osmotic and hypovolemic thirst? What about the functions of the other cell types they found in their analysis? How do these different neuronal populations interact to produce different behavior output? This paper provides the first steps towards dissecting the specific molecular and cellular mechanisms that govern the intricacies of thirst. So next time you reach for a glass of water, ask yourself - why are you actually thirsty, and what part of your brain is responsible for this?

Edited by Gabriella Muwanga.