The mystery of quenching thirst solved

When one feels thirsty, one drinks water. A few gulps down, thirst is quenched and drinking stopped. It may seem as simple as that. But in reality, the mechanisms that are involved in the brain detecting thirst, leading to its quenching subsequently, are rather complicated.

Now, a team, in which a young Indian research scholar played a pivotal role, has unravelled the puzzle. More importantly, they also found why quick gulping rather than sipping helps one quench thirst better.

Vineet Augustine, a graduate student at the lab of neurobiologist Yuki Oka at the California Institute of Technology, US, said, “Though thirst is experienced by every living organism, we almost know nothing about it.”

Sensing thirst

Augustine has been the first author of a study which for the first time created a high-resolution map of the wiring inside the brain’s thirst centre. The paper appeared in the journal Nature on Thursday. “We, for the first time have convincingly showed how a region in the brain called the Median preoptic nucleus (MnPO) integrates signals from the blood content sensors and triggers drinking. If the MnPO is not functioning, even though the brain can detect thirst, the animal will not ‘experience’ thirst and thus will not drink,” said Augustine.

MnPO is one of the three nuclei of lamina Terminalis, the principal brain structure responsible for gauging and regulating internal water balance. MnPO, together with the subfornical organ (SFO) and the organum vasculosum lamina terminalis (OVLT) form the thirst circuit of the brain.

The brain senses the need for drinking water when the salt content in the blood goes up. In no time, it sends out signal to initiate drinking. But what is more significant about their study was another remarkable finding. It actually resolved how the brain sends a subsequent message which initiates the stoppage of drinking.

“An important aspect of thirst is its quick quenching. When you feel thirsty, you drink a glass of water. The water travels from the mouth to your stomach and you feel satiated,” said Augustine, who moved Caltech after a Masters from the Indian Institute of Science Education and Research (IISER) Kolkata.

Gulps not sips

Interestingly, the body takes a good 15 to 30 minutes even to start absorbing water into the bloodstream. In another words, the brain cannot bank upon the blood content sensors to send out the second set of commands, that is to tell the body to stop drinking. “If it does, every thirsty person would be overdrinking. But we all know that we drink only for a few seconds,” said Augustine.

In another words, the brain needs an altogether different mechanism to signal stop drinking. This led Augustine and other researchers in Oka’s lab to the discovery of a set of inhibitory neurons within MnPO that signal to stop drinking. “When activated, these neurons prevent a dehydrated mouse from drinking,” said Augustine, who hails originally from Kerala.

Using state-of-the-art brain manipulation and imaging techniques, the researchers showed how suppressed the thirst driving neurons. The most surprising finding was that these neurons calibrate thirst by measuring the gulping action accompanied by drinking.

“When you are really thirsty, you don’t drink water in sips, you gulp it down, and when you are gulping, the throat moves in a particular way. We hypothesised that this motion of rapidly ingesting water is what the inhibitory neurons are responding to and indeed, we found that the inhibitory neurons are not activated when mice drink water intermittently, simply taking a few sips,” he said.

They also found that these inhibitory neurons are not activated when the animals that are thirsty chew water in a gel form. They responded only to fluids that are gulped. “These neurons act like fluid flow-meters that tell the brain when the body has had enough to drink. This circuit may be the reason why the brain knows to stop drinking well before the stomach has fully absorbed the all the water an animal has drunk,” Augustine said.

The findings are important because improper regulation of thirst is a hallmark of many diseases like diabetes, schizophrenia etc. These thirst circuits are also very closely associated with the regulation of blood pressure.

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