Chronic Stress Induces Activity, Synaptic, and Transcriptional Remodeling of the Lateral Habenula Associated with Deficits in Motivated Behaviors.

Chronic stress (CS) is a major risk factor for the development of depression. Here, we demonstrate that CS-induced hyperactivity in ventral tegmental area (VTA)-projecting lateral habenula (LHb) neurons is associated with increased passive coping (PC), but not anxiety or anhedonia. LHb→VTA neurons in mice with increased PC show increased burst and tonic firing as well as synaptic adaptations in excitatory inputs from the entopeduncular nucleus (EP).