SICKNESS ENGRAMS MODULATE ANTICIPATORY IMMUNE RESPONSES

A threat to survival in the wild is vulnerability to infection. The immune system is essential for defence against foreign species such as parasites, bacteria and viruses, which cause sickness. During infection the brain orchestrates an evolutionarily conserved set of behaviors, including fever, tiredness and loss of appetite that support an immune response. The immune system stores information on previous infections via adaptive immune memory, however it remains unclear whether the brain stores immune-related information from infections as long-term memory engrams. Here, we demonstrate that mice form contextual memories for sickness events. Upon sickness-memory recall mice downregulate their whole-body metabolism, and display increased coactivation between the hippocampus and classical sickness regions such as the central amygdala, alongside elevated engram activation. Optogenetic reactivation of sickness engrams induced a decrease in whole-body metabolism, comparable to that observed during natural recall. Finally, both natural recall and artificial reactivation of a sickness memory was sufficient to increase genes associated with the acute phase response to infection in the liver. Together, these findings suggest that sickness experiences are encoded as engrams, which upon reactivation trigger coordinated metabolic and immune responses.