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bioRxiv · 10.64898/2025.12.23.696158

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

Narain, P.·Susic, M.·Petkovic, A.·Saldi, G.-A.·Arnoux, M.·Sultana, M.·Belete, B. A.·Chaudhury, D.
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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.

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Narain, P., Susic, M., Petkovic, A., Saldi, G.-A., Arnoux, M., Sultana, M., Belete, B. A., Chaudhury, D.. 2025-12-25. Distinct depressive-like behavioural phenotypes in mice exhibit unique patterns of transcriptional perturbations across habenular cell subtypes. https://doi.org/10.64898/2025.12.23.696158

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