Scientists have identified the neurons that effectively govern the instinct of thirst

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Thirst—the basic instinct to drink water—regulates the salt and water balance (osmolality) in the body.

The brain senses changes in this balance and directs us to drink water when needed. Certain medications and conditions, as well as aging, can interfere with this sensor system. In these cases, people become less likely to notice their thirst and may not drink fluids when needed.

Previous studies have shown that the urge to drink water is encoded in the hypothalamus and associated structures called circumventricular organs.

One of these, called the subfornical organ (SFO), is among several regions activated by water deprivation. The SFO lacks the normal blood–brain barrier, so researchers thought it might function as the brain’s osmolality sensor.

A research team led by Drs. Yuki Oka and Charles S. Zuker at the Columbia University Medical Center explored whether neurons in the SFO play a role in controlling drinking behavior.

They used a technique called optogenetics, which uses light to activate or inhibit specific neurons. The research, published online in Nature on January 26, 2015, was partly funded by NIH’s National Institute on Drug Abuse (NIDA) and National Institute of Neurological Disorders and Stroke (NINDS).

The researchers identified 3 distinct types of cells in the SFO of mice: one that expresses proteins characteristic of excitatory neurons; one that expresses proteins characteristic of inhibitory neurons; and a third that expresses proteins found in neuronal support cells called astrocytes.

When the researchers use optogenetics to specifically activate the excitatory neurons, the mice promptly started drinking water, even when they were already well hydrated. Stimulating these neurons didn’t increase consumption of food or other liquids like mineral oil or honey, showing that those neurons promote thirst specifically.

The light-stimulated animals refused to drink water, however, if it contained a bitter compound or high concentrations of salt, showing that these neurons don’t bypass the animal’s aversion to toxic or noxious chemicals.

Activating inhibitory neurons, on the other hand, caused thirsty mice to stop drinking water. Stimulating these neurons didn’t decrease eating in hungry mice or salt consumption in salt-deprived mice. This suggests that the inhibitory neurons of the SFO function as an “off switch” specifically for water consumption.

Together, these findings show that the SFO is a dedicated brain system for thirst. To better understand how the SFO drives drinking behavior, future studies will look at the connections between the SFO and other brain regions activated by dehydration.

“The SFO is one of few neurological structures that is not blocked by the blood-brain barrier—it’s completely exposed to the general circulation,” says Oka, who recently moved to the California Institute of Technology. “This raises the possibility that we may be able to develop drugs for conditions related to thirst.”

In a paper appearing online Thursday in the journal Science, researchers from Stanford University looked at the median preoptic nucleus — a region of the brain that previous research had suggested was linked to the sensation of thirst. However, the exact mechanism behind the link was not understood.

Drinking WaterA volunteer drinks water after fighting a forest fire in the northern area of Brasilia’s National Park in Brazil, Aug. 30, 2017. Photo: Reuters/Ueslei Marcelino

The Stanford team of researchers looked at the RNA expression within the median preoptic nucleus, which apart from thirst is also involved in other functions like regulation of sleep and response to decrease in the body’s core temperature. Mice were deprived of water for 48 hours and a cluster of neurons that got excited as a result was identified as an area of interest.

Next, the scientists inhibited these neurons from firing using optogenetics, and found the mice reduced their intake of water correspondingly. By contrast, when the same neurons were photoactivated, even in mice that had already had their fill of water, the animals drank more water.

Some mice were trained to press a lever that would provide them access to water, and testing various permutations, the scientists found that “the rate of lever-pressing corresponded with a decrease in neural activity over time,” which suggested that neuron activity in the median preoptic nucleus adjusts over time depending on the amount of water intake.

However, the feeling of artificially created thirst by firing neurons was still considered an aversive state by the mice. Researchers found that “mice provided an opportunity to shut off photoactivation of MnPO [median preoptic nucleus] neurons by lever pressing did so vigorously, ending the undesirable feeling of thirst,” a statement by the journal said Thursday.

“When thirsty, animals perform actions that lead to water consumption, which reduces the aversive MnPO activity by some amount. These actions are repeated until enough water is consumed that the level of aversion ceases to evoke behavior. In doing so, an association is formed between particular actions and reduction of an aversive state, which would contribute to making those actions more likely to be repeated when the animal is thirsty again in the future,” the researchers wrote in the study.

Thirst NeuronGenetic targeting of thirst-association neurons in the Median Preoptic (MnPO) nucleus of the hypothalamus following water deprivation. Photo: William E. Allen, Liqun LuoBased on the variety of other brain regions that the MnPO thirst neurons are connected to, as identified in their research, the Stanford team said the instinct of thirst could translate into “specific goal-directed actions.”

The research, however, does not suggest it is healthy or wise to artificially control your thirst by firing the responsible neuron cluster in your median preoptic nucleus. So at least for now, if you are thirsty, just drink some water.

The paper is titled “Thirst-associated preoptic neurons encode an aversive motivational drive” and an abstract can be read here.

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