Thirst Drinking Water

Researchers at the Tokyo Institute of Innovation (Tokyo Tech) offer much deeper insights into neural thirst control. Their study released just recently in Nature Communications indicates that cholecystokinin-mediated water-intake suppression is managed by two neuronal ‘thirst-suppressing’ sub-populations in the subfornical organ in the brain; one population is constantly triggered by extreme water levels, and the other, transiently after drinking water.

Water sustains life on earth. The very first life originated in an ancient sea, and since then, almost every types that has actually existed in the past or lives today depends on the precise balance of salt and water (~145 mM; called body-fluid homeostasis or salt homeostasis) for survival.

The human body has a number of elaborate systems to make sure we take in a suitable quantity of water for maintaining the homeostasis, which is requisite to survival. One of these easy however key “hacks,” is thirst. When the body experiences dehydration on a hot day (noted by the excess of sodium in the body compared to water, a condition called hypernatremia), the brain sends “signals” to the rest of the body, making us yearn for the tall glass of water. On the other hand, under a condition called hyponatremia, where there is a more water than sodium, we reduce water drinking. The neural systems of how this takes place are a topic of fantastic interest.

Neurobiology of Thirst

Two groups of CCK positive excitatory nerve cells were recognized in the SFO that are associated with main thirst-suppressive systems. The activation of these CCK-positive nerve cells reduced water intake, and in an opposite way, their inhibition induced water consumption even under the water-repleted condition. Credit: Tokyo Tech

A team of scientists from Tokyo Institute of Technology, headed by Prof Masaharu Noda, have actually conducted extensive research into this. In their previous research studies, they determined that thirst is driven by the so-called “water nerve cells” in the subfornical organ (SFO) of the brain, a region simply outside the blood-brain barrier. When the body is dehydrated, the plasma levels of a peptide hormonal agent called angiotensin II boost. These levels are detected by special angiotensin II “receptors” of water neurons to promote water intake. In turn, under sodium-depleted conditions (where there is more water than sodium), the activity of these water neurons is reduced by “GABAergic” interneurons. “The latter control appeared to be based on the hormonal agent cholecystokinin (CCK) in the SFO. However, the CCK-mediated neural systems underlying the inhibitory control of water intake had not been elucidated so far,” specifies Prof Noda.

Now, in their newest study published in Nature Communications, the researchers find out more details about this mechanism. They carried out an array of experiments consisting of transgenic mice studies, single cell characteristics, fluorescence microscopic Ca 2 imaging, and optical and chemogenetic silencing to check out the neurons in the SFO.

They made numerous interesting observations: first, CCK was produced in the SFO itself, by CCK-producing excitatory nerve cells, which trigger the GABAergic interneurons through their “CCK-B” receptors, triggering them to suppress the water neurons and hinder thirst. What’s more, there are 2 distinct subpopulations of these CCK nerve cells. Group 1, which is the largest population, shows strong and sustained activation under the Na-depleted condition (excessive water in the body). Group 2 shows a more rapid and short-term activation in reaction to water intake, with the activation lasting no longer than 20 seconds. There are hints of a third group also, but these neurons don’t reveal activation in either condition.

Prof Noda is delighted about the ramifications of this study. “Because CCK has actually long been noted for being an intestinal hormonal agent, these findings open lots of possibilities, the most amazing one being the probability of a negative feedback control of drinking based upon water picking up signals from the oropharynx or gastrointestinal system,” he reports.

The research study highlights the roles of CCK in both Group 1 blood-mediated “consistent” and Group 2 oropharyngeal/ gastrointestinal “transient” suppression of water intake. The potential of CCK to trigger CCK-B receptor-positive various GABAergic interneurons in a cell-type particular way underlies the system for the performance of neuronal circuits. Overall, this research study has actually enhanced the understanding of the “thirst control” phenomenon significantly.

Referral: “Distinct CCK-positive SFO nerve cells are associated with consistent or short-term suppression of water intake” by Takashi Matsuda, Takeshi Y. Hiyama, Kenta Kobayashi, Kazuto Kobayashi and Masaharu Noda, 10 November 2020, Nature Communications
DOI: 10.1038/ s41467 -020-19191 -0

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