The neural mechanism that signals thirst and the thirst inhibitory neurons which signal to stop drinking have been deciphered. The research unravels how the thirst inhibitory neurons signal to stop drinking based on the speed of intake of the liquid. It responds to intake of only liquids.

Wonder why both animals and humans tend to gulp water or drink water very rapidly when thirsty? Apparently, the speed of fluid intake inhibits the thirst neurons, which get activated when a person is thirsty, leading to feeling of satiation.

The feeling of thirst arises when the volume of blood reduces or when salts such as sodium and potassium are high in the blood. Though it takes over 15 minutes for the water to be absorbed into the blood, the brain signals to stop drinking after a few gulps though the water has only reached the stomach.

Now researchers know the reason why we do so. Vineet Augustine, an IISER Kolkata student and now a Ph.D scholar at the California Institute of Technology, Pasadena, California, and others found that certain inhibitory neurons calibrate thirst by measuring the gulping action that accompanies drinking. They have also found the brain mechanism responsible for signalling thirst.

“We found that the inhibitory neurons which signal to stop drinking are not activated when mice drink water intermittently, simply taking a few sips. Nor are they activated when the animals chew water that is in a gel form (98% water) or eat watermelon, which has over 80% water; unlike liquids, it takes longer to ingest a solid. They respond only to fluids that are gulped,” says Mr. Augustine, who is first author of a paper published in Nature.

The inhibitory neurons get activated only when the animals drink any liquid and the neurons respond based on the speed of intake of the liquid. “The inhibitory neurons function as a flow-meter and get activated based on the rate of ingestion, regardless of the total amount of water consumed,” says Mr. Augustine.

Interestingly, the inhibitory neurons, which signal to stop drinking, do not discriminate between water and other fluids such as saline or even silicone oil. “Animals stop feeling thirsty, at least for some time, immaterial of the liquid taken in,” he says. Unlike other liquids, the intake of water evokes an additional inhibitory effect that persists after drinking episodes. This explains why we don’t feel thirsty soon after drinking water.

Thirst neural circuit

The researchers first identified the thirst circuits in the lamina terminalis, the principal brain structure responsible for sensing and regulating internal water balance. There are three nuclei — the SFO, the organum vasculosum lamina terminalis (OVLT) and the MnPO — which form the thirst circuit and are interconnected.

“The SFO and OVLT are regions in the brain which have leaky blood-brain barrier. So they are in direct contact with blood circulation and help in sensing low blood volume and signal for thirst,” says Mr. Augustine. The researchers found that when SFO or MnPo is excited animals start drinking water.

Thirst hierarchy

There is a hierarchy neural organisation with the SFO and OVLT sending signals to MnPO, which is at the top of the hierarchy. “The way the circuit works is that whenever there is less water in the blood, the SFO and the OVLT detect and signal the MnPO, where the signal integration happens and the animal feels thirsty and starts drinking water.

Within the MnPO, a set of thirst inhibitory neurons sends the inhibitory signal to the SFO nuclei to stop drinking. When the researchers activated the MnPO inhibitory neurons, a dehydrated mouse stopped drinking. “Using state of the art tools, we showed that MnPO inhibitory neurons suppress the thirst-driving neurons,” he says.

This research has far reaching consequences as improper regulation of thirst is a hallmark of many diseases such as diabetes. These thirst circuits are also very closely associated with the regulation of blood pressure.

Published in The Hindu on March 1, 2018