How do we know when we are thirsty and when our thirst is sated? Thirst is regulated by nerve cells in the brain, which can stimulate and stifle the desire to drink. Scientists at Caltech have now mapped the circuitry of neurons that control the process in the brains of mice. This study, published in Nature, provides insight into how mammals and potentially humans regulate thirst.
In the mouse brain, three areas are known to be involved in thirst; the SFO or subfornical organ, the OVLT or organum vasculosum laminae terminalis, and the MnPO, median preoptic nucleus. They create a structure in the forebrain like a sheet, the lamina terminalis (LT). While most areas in the brain are shielded behind the almost impervious blood-brain barrier, the SFO and OVLT directly interact with the bloodstream in the mouse. Thus, the brain can sense sodium levels in the blood, which indicates how well the body is hydrated. That makes the LT the primary player in sensing hydration levels, and therefore, thirst regulation.
This work was led by Yuki Oka, assistant professor of biology, who has previously shown that regions in the LT contain excitatory neurons that can initiate drinking when stimulated. The study, reported in Nature, reveals how the various kinds of excitatory neurons in the LT mold the circuitry that drives drinking.
The MnPO region, in particular, was found to be central to regulating thirst. For one, the SFO can send the MnPO excitatory signals, but the signals don’t go in the other direction. Additionally, when excitatory MnPO neurons are silenced, stimulation of the SFO and OVLT doesn’t cause drinking. A hierarchical relationship is thus revealed. Thirst signals from the SFO and OVLT are integrated in the MnPO, which then sends them along to get drinking started.
"When you are dehydrated, you may gulp down water for several seconds and you feel satisfied. However, at that point your blood is not rehydrated yet: it usually takes about 10 to 15 minutes. Therefore, the SFO and the OVLT would not be able to detect blood rehydration soon after drinking. Nevertheless, the brain somehow knows when to stop drinking even before the body is fully rehydrated," said Oka.
Because of the discrepancy between rehydration and satiety signals in the brain, the researchers reasoned that a rapid signal must be stifling drinking behavior.
The investigators learned that some of the inhibitory neurons in the MnPO instantly respond to drinking activity, directly inhibiting SFO thirst neurons. Liquid activates them specifically, while solids don’t. The researchers suggested that the intake of fluids is monitored by the inhibitory through movement of the throat as it swallows, which precisely inhibits the thirst neurons.
"When you are really thirsty and quickly gulp down fluid, the throat moves in a particular way that is different from eating food," explained lead author of the report and graduate candidate Vineet Augustine. "We think the inhibitory population is responding to this motion of rapidly ingesting water."
Although inhibitory neurons in the MnPO may relate to thirst inhibition, the research team suggested that the brain has additional signals for satiety.
"The inhibitory signals we discovered are only active during the drinking action," said Oka. "However, the feeling of satiety indeed lasts much longer. This indicates that the MnPO inhibitory neurons cannot be the only source of thirst satiety. This will be the subject for future study."
The investigators also identified another circuit involved in the relief of thirstiness. While these findings were in mouse brains, there are similar areas in human brains. The scientists note that a similar circuit may exist in humans.