How the gut controls thirst
Image: Neurons that control thirst in the mouse brain are switched on (green and red) when the gut senses salty fluid. [Knight lab]
Using microendoscopic imaging, US-based researchers have worked out how the body signals thirst to the brain.
By tracking neural activity in living mice, Howard Hughes Medical Investigator Zachary Knight, a neuroscientist at the University of California, San Francisco, and colleagues, watched in real time how the gastrointestinal tract measures the salt concentration in the intestines and relays this information directly to the brain.
“It had been something we just couldn’t explain,” says Knight. “How does the brain know so quickly whether thirst has been quenched?”
To gain insight into this vexing question, Knight and colleagues set out to monitor the dynamics of thirst-promoting neurons in the brain while manipulating the fluids that were ingested or infused into the peripheral tissues of a mouse.
In earlier research, Knight and colleagues had used fibre photometry to record the activity of a specific set of neurons associated with thirst.
Here, an optical fibre was threaded into the brain and the researchers watched as these neurons rapidly switched off when dehydrated mice took a sip of water or saline.
Importantly, results revealed that if the mice had drank the salt water, the neurons were only switched off for a short time.
To investigate this effect further, the researchers inserted intragastric catheters into the mice, to control fluid flow into the stomach.
They then added fibre photometry implants to the mice to monitor neuron dynamics as fluid was ingested.
In a series of experiments, they showed that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice.
“What’s stunning about the finding is that the gut can so precisely measure salt concentration,” says Knight.
The researchers used microendoscopic imaging to investigate how these neurons encode aspects of fluid balance.
As Knight says: “We show that individual neurons compute homeostatic need by integrating gastrointestinal osmosensory information with oropharyngeal and blood-borne signals.”
The researcher reckons that pairing neural recordings in living animals with techniques for manipulating the body has proven critical to observing brain behaviour.
“This is a prototype of the kind of science we’re going to be doing in my lab in the years to come,” he says.
Research is published in Nature.