When we’re feeling under the weather, we tend to eat, drink, and move less. And we’re not the only ones; when an illness is present, these three actions are often reduced in most species. A recent study has identified the network of neurons responsible for these responses, often known as illness behaviors. Researchers showed that a particular group of cells in the brainstem may potently create three hallmark symptoms of illness by inducing immunological responses in mice. Inhibiting these neurons also reduces the severity of each of these behavioral manifestations of the illness response. The findings, which were reported in Nature, reveal a clear connection between inflammation and the neuronal circuits that control behavior and shed light on how the immune system communicates with the brain.
According to Jeffrey M. Friedman, the Marilyn M. Simpson Professor at The Rockefeller University, “We are still in the early stages of trying to comprehend the brain’s function in infection.” But now that we have these findings, we have a rare chance to inquire, “What does your brain look like when you’re sick?”
It has been demonstrated that illness behaviors are crucial to an animal’s ability to recover from an infection. That theory has been supported by earlier research showing a markedly increased mortality in animals forced to eat when ill. The main author of the study, Anoj Ilanges, who used to be a graduate student in Friedman’s lab and is now a group leader at the HHMI Janelia Research Campus, says that these changes in behavior during infection are important for survival.
But how the brain cells links the almost ubiquitous inclination to skip meals and stay in bed with the onset of an infection has never been fully understood. Therefore, Friedman and Ilanges set out to map the mouse brain areas responsible for ill-behaving behaviors.
In order to stimulate the immune system and effectively create illness behavior in mice, the research team first exposed the animals to LPS, a component of bacterial cell walls. A group of neurons expressing the neuropeptide ADCYAP1 had an increase in activity shortly after an injection of LPS in the dorsal vagal complex, a region of the brainstem. The scientists then turned on those neurons in healthy mice to check that they had discovered the correct brain cells, and they discovered that the animals ate, drank, and walked about less. When the ADCYAP1 neurons were turned off, however, LPS had much less of an effect on these behaviors.
Friedman says, “We found it interesting that a single neural population seemed to regulate each of these components of the sickness response. We didn’t know if the same or separate neurons regulated each of these actions.
However, the fact that this brainstem region was instrumental in mediating pathological behaviors did not entirely surprise the authors. One of the rare physiological intersections of the central nervous system where the blood brain barrier does not exist and allows circulating blood components to transmit information directly to the cells is the dorsal vagal complex. According to Friedman, “This region has become a sort of alarm center for the brain, communicating information about unpleasant or noxious chemicals that, more often than not, lower food intake.”
In the upcoming months, Friedman’s group at Rockefeller University plans to integrate these discoveries into their overarching objective of comprehending the physiological signals and neuronal circuitry that control feeding behavior. They are especially interested in finding out why mice that have been raised to eat a lot stop eating when they get sick from bacteria.
When Ilanges investigates the role that other brain regions play in responding to infections, we will learn more about the function of the brain during this important phase. We only focused on one area of the brain, but the immune response activates numerous other areas as well, he claims. This lets scientists look into how the brain works as a whole when it has an infection.
