How does thirst work in the brain?

Here in the UK, we’re told to drink 6-8 glasses of water a day. But then chances are you’ve got a caffeine hit or two, maybe you have a fruit juice, a fizzy drink, some squash, the list goes on. And Naked Scientist Eva Higginbotham spoke to Princeton’s Christopher Zimmerman, who has recently been awarded the Eppendorf and Science Prize for Neurobiology for his essay describing his breakthrough research into the science of thirst, which has been upending the textbooks...

Christopher - My research asks a really simple question, which is, "how does the brain produce the sense of thirst? And how does it use this information to control our drinking behaviour"? There's a small group of cells located deep in the brain that we call osmosensors. And we call them osmosensors because they can sense changes in the osmolarity or the concentration of molecules and salts in our blood. And these changes in osmolarity are the main hallmark of dehydration.

From our understanding of these cells, we would say that the sensation of thirst is just how hydrated we are at any one given point in time, how changes in blood osmolarity are occurring. But we know from introspection and from a lot of research that that's not actually how we feel thirst. For example, when we've been quite thirsty or dehydrated, maybe after exercising and we drink water, our thirst is quenched almost immediately, even though that water won't actually enter the bloodstream and correct our deficit for many minutes. And it's really been unknown how the brain solves this problem.

We reasoned that what we needed to do is record the activity of these thirst located deep in the brain. Obviously this would be very challenging in humans. So we used mice just study this problem who have very similar brain structures and also drinking behaviour to humans. And we use new tools in neuroscience that allow us to put a fiber optic cable in the animal's brain and then record the activity of these cells in real time, as a mouse is freely behaving, so it can walk through its environment and eat, and drink and do anything it likes, and we can ask what these neurons care about as it does that.

Eva - And what did you find?

Christopher - So the first thing we found was that these neurons are osmosensors. If the osmolarity of the blood increases, the activity of these cells increases, and that makes the animal feel thirsty. What was really surprising is that for example, when the animal then went and drank water, rather than slowly turning off as the water entered the bloodstream, these neurons turned off almost immediately a little bit with every gulp or lick that the animal took, in a way that counted how much the animal is drinking. So they seem to be getting some anticipatory or predictive signal from elsewhere in the body that was letting them predict how the water would affect hydration in the future.

Eva - So it seems like really direct feedback then. How is it that they taste the water and immediately the brain is saying, "alright, we're getting some of what we need right now"?

Christopher - It's really interesting. There seem to be layers of signals that arise from different parts of the body as we drink. So for example, there's a first signal that comes from the mouth and throat that signals exactly how much. So the volume that we've consumed. And this involves as far as we can tell a number of sensory properties, including the temperature of the mouth, and maybe swallowing as well. And then there's another signal that arises a little bit later from the gut, from our stomachs and intestines, that tells these cells in the brain, not how much we drank, but what we drank. So was it pure water or how salty was it? And they can use this information to then decide how thirsty we should be in the future.

Eva - So how do you think these signals work?

Christopher - Yeah, that opens a really interesting set of questions to address moving forward. We never knew these signals existed before, and it's been really interesting to see how they affect our behaviour. But it also suggests that there are cells and molecules in our periphery - so in our mouth and throat and gut - that are initiating them. So cells in our mouth that express a protein that lets them sense water or fluids. Cells in the gut that express some protein that lets them sense osmolarity. And then neurons that take this information from those distal parts of ourselves and send it to the brain. And we're really only beginning to understand those pieces in this system and looking for and identifying them is going to be really exciting in the near future.