A Gut Feeling: Zachary Knight Discovers That Thirst is Controlled by Signals in the Gastrointestinal Tract

The Context: The brain has “thirst neurons” that help us know when we need water and when we don’t. But how these neurons receive information from the body about whether thirst has been quenched was previously unknown. 

The Study: The neurons in the brain that control thirst respond to signals sent from the gut according to a new study in Nature from researchers at the University of California, San Francisco led by NYSCF – Robertson Neuroscience Investigator Dr. Zachary Knight. 

The Importance: This study uncovers a new way in which the gut talks to the brain and gives insight into the complex processes that help our bodies maintain balance (homeostasis).

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After going for a long run, you will likely crave a satisfying swig of water. But after just a few gulps, the craving is gone. How does the body know so quickly that your thirst has been quenched? According to a new study in Nature from researchers at the University of California, San Francisco (UCSF) led by NYSCF – Robertson Neuroscience Investigator Dr. Zachary Knight, the answer lies in the gut.

Our brains contain “thirst neurons” whose activity tells us when we are thirsty and when we are not. But the root of thirst lies in the body, not the brain, so there needs to be some sort of signal from the body that tells the thirst neurons when to start firing.

Previous research from Dr. Knight’s lab has suggested that this signal comes, in part, from the throat. In a 2016 experiment, the team watched a set of thirst neurons in the brains of mice and found that when thirsty mice took a sip of water and the liquid hit the mouth and throat, thirst neurons turned off. What puzzled the scientists, however, was that a drink of salt water (which does not rehydrate the body), turned the thirst neurons off too, but only temporarily.

“It’s like there’s another signal telling the thirst neurons, ‘This is not rehydrating you,'” said Dr. Knight in a press release from UCSF.

The team suspected that perhaps this second signal was being sent from the gut. In their current experiment, the team infused the guts of mice with plain water or salt water. Plain water quickly shut the thirst neurons off, but the salt water kept them active. This suggests that the gut contains a type of “sensor” that sends a signal to the brain to say “thirst has been quenched” or “seek more water.”

By taking a closer look at neurons in the brain, the team found that single neurons in a part of the brain called the median preoptic nucleus are the ones responsible for integrating the information from the throat, blood, and gut to evaluate thirst.

“The body’s thirst-sensing system is relatively simple,” Dr. Knight says. “Working out its details could eventually help scientists figure out more complicated systems, like feeding and regulating body temperature.”

The experiment’s method of recording neural activity in living animals while manipulating the body proved to be an insightful way to observe the connection between brains and behavior. Dr. Knight is looking forward to using similar techniques in the future.

“This is a prototype of the kind of science we’re going to be doing in my lab in the years to come.”

A gut-to-brain signal of fluid osmolarity controls thirst satiation

Zimmerman CA, Huey EL, Ahn JS, Beutler LR, Tan CL, Kosar S, Bai L, Chen Y, Corpuz TV, Madisen L, Zeng H, Knight ZA. Nature. March 27, 2019. doi: 10.1038/s41586-019-1066-x