Nature: Why do you just want to lie down when you're sick?

When we feel uncomfortable, we tend to eat less, drink less, and exercise
less.
This is not unique to humans – most animals reduce these three behaviors
when fighting infection.

Now, a new study pinpoints the clusters
of neurons that control these responses (undesirable behaviors).
By stimulating an immune response in mice, the researchers demonstrated that specific cell populations in the brainstem could effectively induce three suggestive uncomfortable behaviors
.
In addition, inhibition of these neurons weakens each behavioral element
of the uncomfortable response.

The study, published in the journal Nature, directly links inflammation to neural pathways that regulate behavior, providing insight into how the immune system interacts with the brain
.

Professor Jeffrey M.
Friedman of The Rockefeller University said: "We are still in the early stages
of trying to understand the brain's role in infection.
But with these results, we now have a unique opportunity to ask: What does your brain look like when you're sick? ”

Sickness behavior has been shown to play an important role
in helping animals recover.
Previous studies have confirmed that forcing animals to eat when they are sick significantly increases mortality
.
"These behavioral changes during infection are really important for survival," said first author Anoj Ilanges, a former graduate student in Friedman's lab who now works at
the Howard Hughes Medical Institute.

However, it has not been clear how the brain coordinates this relationship, that is, not wanting to eat after an infection and just wanting to hide under
the covers.
So Friedman and Ilanges set out to map the brain regions
behind the mice's uncomfortable behavior.

The team first exposed mice to lipopolysaccharide (LPS), a component in bacterial cell walls that activates the immune system and effectively induces uncomfortable behavior
.
Shortly after LPS injection, activity in the dorsal complex region of the vagus nerve in the brainstem surges, and these neurons express the neuropeptide ADCYAP1
.
To confirm that they had found the right brain cells, the researchers then activated these neurons in healthy mice, and they found that the mice ate, drank, and walked around
less.
Conversely, when ADCYAP1 neurons were inactivated, the effect of LPS on these behaviors was significantly reduced
.

"We don't know if it's the same neuron or different neurons that control each behavior," Friedman said, "and we were surprised to find that a single population of neurons seemed to regulate every component of
the discomfort response.
" ”

Still, the researchers weren't surprised
that this brainstem region was involved in regulating uncomfortable behavior.
The dorsal vagus complex is one of the few crossroads in the central nervous system, where there is no blood-brain barrier and circulating factors in the blood can transmit information directly to the brain
.

"This region has become a kind of alarm center in the brain that transmits information about antipathy or toxic substances, leading to a reduction in the intake of related foods," Friedman said
.

In the coming months, Friedman's team at The Rockefeller University intends to incorporate these findings into their overall goal of understanding the physiological signals and neural circuits that regulate eating behavior
.
They were particularly interested in why engineered gluttonous mice also stopped eating
when they were infected with bacteria.

At the same time, Ilanges plans to study the role
other areas of the brain play in responding to infections.
"We looked at one area of the brain, but there are many other areas that are activated with the immune response," he says
.
"This opens the door to understanding what the brain is doing
in general during infection.
"

Original text search

Ilanges, A.
, Shiao, R.
, Shaked, J.
et al.
Brainstem ADCYAP1+ neurons control multiple aspects of sickness behaviour.
Nature 609, 761–771 (2022).
https://doi.
org/10.
1038/s41586-022-05161-7