Humans can typically survive only three to five days without water. But we’ve all said “I’m dying of thirst” well before we’ve been waterless that long – albeit with little understanding of the mechanism behind the urge. But now the brain signals that govern thirst are no longer a mystery. A team led by HHMI Investigator Charles Zuker has figured out that the motivation to drink water is controlled by two sets of neurons: one that provokes the stimulus to sip and one that quenches it.
Researchers have long suspected that the signals driving animals to drink originate in the brain’s subfornical organ, or SFO. Located outside the blood-brain barrier, where it has the opportunity to directly sense the electrolyte balance in body fluids, the SFO shows increased activity in dehydrated animals. Yuki Oka, a postdoctoral fellow in Zuker’s Columbia University lab, took a closer look at the SFO in mice and identified two types of nerve cells: excitatory CAMKII-expressing neurons and inhibitory VGAT-expressing neurons. Using optogenetics, Oka added a light-sensitive protein to the cells in the animals’ SFOs, allowing him to selectively activate them with blue light. When he flipped the switch and activated the CAMKII neurons, the rodents drank with gusto.
|When stimulated with blue light, mice drink with zeal, even if the water is presented in an unfamiliar bowl.|
“You have a water-satiated animal that is happily wandering around, with zero interest in drinking,” says Zuker. “Activate this group of SFO neurons, and the mouse just beelines to the water spout. As long as the light is on, that mouse keeps on drinking.” Oka showed that the animals became such avid drinkers that they consumed as much as 8 percent of their body weight in water – the equivalent of 1.5 gallons for humans. When Oka used the same technique to stimulate VGAT neurons, thirsty animals immediately stopped drinking and reduced their water intake by about 80 percent. The researchers published their findings online January 26, 2015, in Nature.
According to Zuker, the opposing neurons likely work together to ensure animals take in enough water to maintain fluid homeostasis, including blood pressure, electrolyte balance, and cell volume. It remains to be seen whether the same circuit controls thirst in humans; if so, the findings could one day help people with an impaired sense of thirst.