Remembering immunity: Neuronal ensembles in the insular cortex encode and retrieve specific immune responses

Increasing evidence indicates that the brain regulates peripheral immunity. Yet, it remains unclear whether and how the brain represents the state of the immune system. Here, we show that immune-related information is stored in the brain’s insular cortex (InsCtx). Using activity-dependent cell labeling in mice (Fos^TRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (DSS-induced colitis and Zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can encode and initiate specific immune responses, extending the classical concept of immunological memory to neuronal representations of immunity.