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Image source: © Jennifer Altman

Thirsty – Lights On!

Explore Life Science

For his PhD, American scientist Christopher Zimmerman studied how neuronal structures influence the behavior of drinking. His findings have since made their way into scientific textbooks.

The human body consists of 70 percent water, carefully calibrated: cells are only able to carry out their tasks if they are surrounded by the right volume and the correct concentration of water molecules. If our fine-tuned fluid equilibrium is under threat, we will experience an unmistakable warning signal – thirst!
Until recently, researchers worked under the assumption that a thirst center, located inside the brain, gave the order to “drink” and that, along the lines of a feedback system, neurons inside the brain would receive information from the circulatory system – for instance “the blood is too salty and too thick!” and that these neurons would subsequently sound the alarms in our brain.

Questions upon questions
The exact location of this area has been known for a long time: the subfornical organ of the third ventricle. However – inconsistencies remained. These were not limited to the physiological questions, such as: why can a cold drink quench thirst as soon as it enters the mouth – long before the liquid reaches the bloodstream? Or: why does thirst appear to be quenched after a few gulps of water, even though this amount cannot possibly be sufficient? Simple behaviors, too, remained unexplained: why do humans (and animals) like to drink with meals?
Christopher Zimmerman spent five years solving this mystery by conducting experiments on mice. It is a good thing that when it comes to drinking, the behavior of mice is analogous to that of humans and that the brain structures are also comparable. His research not only earned him his PhD, but it was also recognized through multiple awards. In 2020, the 31-year-old American scientist was awarded the prestigious “Eppendorf & Science Prize for Neurobiology” for young scientists, worth $25,000.
Image source: © Jennifer Altman
On the right track
Zimmerman reached his goal after navigating an academic detour: “I wanted to be an engineer, and I liked biology” – so he enrolled in the bioengineering program at the University of Pittsburgh in Pennsylvania. During one classroom course, when tasked with understanding the machines and techniques that allow doctors to peer into the brains of human patients, he discovered: “It was the brain itself, rather than the engineering aspect, that I was interested in.” ”For centuries”, so Zimmerman, „it has been a mystery what happens deep inside the brain, but modern tools were finally allowing scientists to study these processes.” Zimmerman’s scientific instinct had been awakened, and as a natural consequence, he switched to the neurosciences. He joined the team of Zachary Knight in San Francisco: “This was where I learned to ask the right questions” – and this was also where he began to address the behavior of drinking.
Zimmerman discovered that neurons within the cerebral thirst center do not act alone – they work as a team, and they are supported by cells from within the body. The scientist identified these cells in various regions of the body, including the oral cavity, the throat and the abdomen. How did he do it? The young graduate student “illuminated” the mice – in particular, their brains. To this end, he employed small fluorescent proteins that he channeled into the thirst center using viruses, also known as vectors. This approach allowed him to monitor when these neurons would become active. He was excited: “It felt as though all of a sudden, I was given permission to peek directly inside the brain.”
Image source: © Jennifer Altman
Knowledge as the reward
The mice, with antennae on their heads, acted as amateur radio operators. When they became thirsty, a light came on. The light also signaled to the scientist which neurons were communicating, and when. “These are the most rewarding moments”, recalls Zimmerman, visibly enthusiastic, “when, looking at the monitor, one suddenly understands something that one had been thinking about for a long time.”
Thanks to the work by Zimmerman’s team, it is now clear that these neurons inside the hypothalamus are flanked by two additional rapid sensory signals. The first signal encodes messages about the amount of drink – irrespective of whether it consisted of silicone oil or salt water. “This finding resulted in the question of where inside the body the nervous system identifies the actual nature of the drink”, says Zimmerman, explaining his thought process.
His team followed a hunch and also prepared the abdomens of the mice with catheters for infusions into the stomach. Lo and behold – they were right: the second signal receives its information from the intestines; it is able to discern whether the mouse had indeed been given water to drink and, if in doubt, also override the first signal (from the oral cavity) – in case the drink had been oil after all. Moreover, Zimmerman discovered that these two newly deciphered signals, which are transmitted from within the body, in fact act in an anticipatory manner, i.e., they predict the hydration level of the blood and are thus capable of prophylactically regulating thirst. This explains the fact that thirst is quenched after only a few gulps, even though it is not yet possible for the liquid to have reached the body’s metabolism.

Visible scientific pride
By now, Zimmerman’s discoveries have been incorporated into scientific textbooks. Put on the spot, he himself describes them as “groundbreaking”, his scientific pride audible. It is also visible – even though he must wear a mask throughout our Zoom interview. The mask does not bother him; handling pathogens in the laboratory on a daily basis, he is used to it. What is worse, though, is the fact that as soon as Christopher Zimmerman arrived at his new place of work at the Ivy League Princeton University in New Jersey, so did the coronavirus: all laboratories were closed, and most of the the mice had to be euthanized.
Scientist through and through – ambitious, meticulous and extremely organized – he continued to further his career despite the lockdown. He loves reading historical research literature as well as retracing the scientific questions of the time. He also acquired new skills which include the management of large datasets.
The American researcher considers his scientific life to be “extremely challenging mentally.” Taking a break from time to time and relaxing is practically a must. For him, this is best achieved in nature while hiking and climbing mountains with his wife, a fellow scientist. “She is an astronomer – that’s much cooler”, laughs Zimmerman.


Click here for the website with more information about Christoper Zimmermann.