How do we know when we’re thirsty, and how do we know when to stop drinking? This is very important, as we need to keep proper concentrations of ions (also known as osmolarity) within the fluid compartments of our body to stay alive. Osmolarity can be thought of as the relative concentrations of ions in a solution, where our body likes to stay around 300 milli-osmoles (mOsm), where each compartment (intra-cellular, interstitial, and blood) remain in equilibrium. If you drink too much water, you can die due to the drastic changes in osmolarity that occur, causing our cells to burst (lysis). If you are dehydrated, our cells wrinkle up (crenation), a phenomenon that can also lead to death. A jarring example of this occurred in 2007 when a radio station held a contest titled “Hold your Wee for a Wii”, where contestants were tasked with drinking as much water as they could without peeing to win a Nintendo Wii. Unfortunately, the radio DJs did not know anything about basic physiology and were under the false impression that you can drink as much water as you want without any detrimental effects. One contestant drank so much that the osmolarity of her blood became drastically different from other fluid compartments in her body leading to cell lysis, and she died as a result.

There are several well-known circuits in the brain that have been identified as key regulators of thirst and drinking behavior. These include the subfornical organ (SFO), the median preoptic nuclei (MnPO), and the supraoptic nuclei (SON). Together, these structures receive input from the mouth and throat on the amount of liquid that we are drinking in real time (that is, they detect the volume of fluid intake), and are rapidly inactivated upon drinking pretty much any type of fluid (See the Figure below). After not drinking for a while (i.e., we’re thirsty), the activity in these structures rises and promotes drinking behavior. There’s something that doesn’t quite add up here, and that is how do these structures know the ‘type’ of fluid that you’re drinking? If it is just measuring the volume, then we’d feel just as quenched after drinking a bottle of sea water as we would after drinking one of fresh water. The only real difference between fresh and sea water is the salt content (that is, sea water has a higher osmolarity than fresh water). That means that there must be an osmolarity detector somewhere in the body that relays to the brain information about the type of fluid that has been consumed. As Dr. Knight says, "There has to be a mechanism for the brain to track how salty the solutions that you drink are and use that to fine-tune thirst…But the mechanism was unknown."