Changes in the timing and location of activity in the brain's emotion control area mark the start of depression-like behaviors

Chronic stress leads to progressively heightened excitatory responses in the lateral habenula of male mice.

• A spatially resolved molecular atlas of the lateral habenula (LHb) reveals organized changes in gene expression following chronic stress.
• Longitudinal imaging shows that excitatory neuronal responses to aversive stimuli increase over time after chronic stress.
• These changes in neuronal activity correspond with the development of depression-related behaviors.
• Administering the antidepressant ketamine reverses the heightened excitatory responses and associated behavioral phenotypes.
• Limiting LHb neuronal activity or administering ketamine early in the process may have antidepressant effects.

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