Spatiotemporal remodeling in habenula marks the onset of depression-related phenotypes.

Spatiotemporal remodeling of LHb gene expression and neuronal activity marks the onset of depression-related phenotypes in male mice after chronic stress.

• Why it matters: Understanding when and how the LHb contributes to depression is crucial for identifying optimal intervention windows, as the timing of stress-related neural changes remains unclear.
• What they did: The study used spatial transcriptomics to create a molecular atlas of the LHb, combined with longitudinal in vivo two-photon calcium imaging of neurons, and tested effects of ketamine and chemogenetic interventions in male mice subjected to chronic stress.
• The result: Findings show gene expression and neuronal responses in the LHb progressively change with stress, paralleling depression-like behaviors, and these changes are reversible with ketamine or neuronal activity limitation, highlighting potential therapeutic targets.