Distinct depressive-like behavioural phenotypes in mice exhibit unique patterns of transcriptional perturbations across habenular cell subtypes

Abstract

Abstract Major depressive disorder arises from diverse neurobiological mechanisms, yet how specific habenular cell types contribute to distinct depressive-like behaviours remains unclear. Using chronic social defeat stress, behavioural phenotyping, and single-cell RNA sequencing, we mapped stress-induced transcriptional changes across habenular cell types and lateral habenula (LHb) subregions. Our findings reveal that each behavioural phenotype is marked by its own transcriptional profile. These subregion-specific patterns across the LHb suggest that different cellular circuits contribute uniquely to depressive-like states.