A new study maps the brain circuits that tell us when we need to drink water, as well as when we have had enough. The research uncovered a neural hierarchy by stimulating and suppressing the urge to drink in mice.
Feeling thirsty is a sensation that everyone and every animal is familiar with.
It is an experience so common that few of us give it a thought. But neuroscientists are fascinated by it.
In relation to the survival of an organism, thirst is incredibly important. An animal that doesn’t take on fluids when it needs them will not be alive for long.
Without water, most of the processes within the body will seize up, and in humans, death follows in a short number of days.
Although the idea that our brains can detect water levels in the body and drive our desire to drink is not new, the exact neuroscience behind it is only slowly being fleshed out.
The most recent study to investigate the thirst mechanism was carried out by Yuki Oka, an assistant professor of biology at Caltech in Pasadena, CA. The findings were published this week in Nature.
Some work has already been done in this area. Studies have shown that a sheet-like structure in the forebrain, the lamina terminalis (LT), is important in thirst regulation. The LT comprises three parts: the organum vasculosum laminae terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus (MnPO).
The majority of the brain is separated from the bloodstream by the blood-brain barrier. Alongside other roles, this membrane protects the brain from pathogens, such as bacteria. But the SFO and OVLT are unusual; they are not protected by the blood-brain barrier and can directly contact the bloodstream.
This direct communication with the blood allows them to assess sodium concentration, so the “saltiness” of the blood is a good indication of how hydrated an animal is.
Earlier work has already shown that the LT contains excitatory neurons. When they are stimulated in a mouse, it elicits drinking behavior.
In this new study, the scientists found that the MnPO is particularly important, in that the nucleus receives excitatory input from the SFO but not vice versa.
They showed that when the MnPO’s “excitatory neurons are genetically silenced, stimulating the SFO or OVLT” no longer produces drinking behavior in the mice.
This study is the first to describe the LT’s hierarchical organization: the MnPO gathers information from the SFO and OVLT and passes it along to other brain centers to trigger drinking activity.
The scientists also go some way toward answering another question regarding drinking behavior: how do we know when to stop? Prof. Oka explains the conundrum, saying, “When you are dehydrated, you may gulp down water for several seconds, and you feel satisfied.”
“However,” he adds, “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.”
This infers that there is another, more rapid signal that informs the brain to stop drinking. Studies have shown that excitatory neurons in the LT are quietened when a mouse begins to drink, but exactly how this occurs is not known.
Prof. Oka and team demonstrated that inhibitory neurons in the MnPO respond to the physical action of drinking and suppress activity in the SFO thirst neurons. Interestingly, the inhibitory neurons only do their job in response to the ingestion of liquids — and not food.
They believe that this distinction between fluids and solids is possible by monitoring the movement of the oropharynx, which is the part of the throat involved in the swallowing mechanism. Its activity when drinking is different to eating.
“When you are really thirsty and quickly gulp down fluid, the throat moves in a particular way that is different from eating food. We think the inhibitory population is responding to this motion of rapidly ingesting water.”
Lead study author Vineet Augustine, a graduate student
The findings add to our understanding of the complex network of interactions that tell us when we need to drink. But, according to the study authors, there is still much to learn.
As Prof. Oka explains, “The inhibitory signals we discovered are only active during the drinking action. 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.”
Of course, the study was carried out in mice, but similar regions can be found in the human brain. The researchers therefore believe that the findings are applicable to us, too.