Distinct Neuronal Populations in the Bed Nuclei of the Stria Terminalis (BNST) Control IL1-β - mediated Stress Responses

Abstract

The immune and nervous systems are intricately linked. However, mechanistic pathways linking cytokine-mediated stress networks in the brain to peripheral immune and cardiac functions remain poorly understood. Here, we identify a specific population of neurons in the bed nucleus of the stria terminalis (BNST), which shape diverse responses to interleukin-1β (IL-1β)-mediated stress phenotype. Using activity-dependent cell labeling in mice, we identify distinct neuronal ensembles in the BNST that are active in response to IL-1β. Interestingly, re-exposure of mice to acute restraint stress results in the labeling of same populations in the BNST that were responsive to IL-1β administration. Chemogenetic reactivation of these IL-1β-responsive neuronal subsets in the BNST is suffcient to broadly retrieve the stress-induced responses. Specifically, reactivation of these IL-1β -responsive neurons in the BNST recapitulates tachycardia and inflammation induced by acute restraint stress, whereas specific ablation of IL-1β-responsive neurons in the BNST attenuates stress-induced serum IL-6 levels and IL-1β-induced tachycardia. Our data define a neuronal population in the BNST that is both necessary and suffcient for mediating IL-1β-associated stress responses, revealing a role for BNST coordination of inflammatory responses. Supported in part by grants from NIH, NIGMS, 1R35 GM118182 to KT and 1R01AR083159-01 to SC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.