Brainstem ADCYAP1⁺ neurons control multiple aspects of sickness behaviour

Area of Science:

• Neuroscience
• Immunology
• Behavioral Science

Background:

• Infections trigger adaptive sickness behaviors like anorexia and lethargy.
• The neural mechanisms underlying these sickness responses remain largely unknown.

Purpose of the Study:

• To identify the specific neural populations controlling sickness behaviors.
• To elucidate the brain's role in orchestrating the diverse responses to infection.

Main Methods:

• Whole-brain activity mapping using FOS expression after LPS treatment.
• Genetic manipulation (TRAP2 mice) to reactivate specific neurons.
• Single-nucleus RNA sequencing to identify neural populations.
• Inhibition of neural activity to assess behavioral impact.

Main Results:

• LPS treatment activated specific neurons in the nucleus of the solitary tract (NTS) and area postrema (AP).
• Reactivation of these NTS-AP neurons mimicked sickness behaviors and fever.
• Inhibition of these neurons reduced all LPS-induced sickness behaviors.
• Activation of ADCYAP1+ neurons in the NTS-AP fully recapitulated LPS effects.

Conclusions:

• A specific NTS-AP neural population is necessary and sufficient for sickness responses.
• This study establishes a critical link between brain function and the host's response to infection.