• Lateral Habenula in depressive disorders

JOAQUIN PIRIZ

Porto Alegre

Conferencia; Seminarios Departamento de Bioquímica UFRGS; 2011

Universidade Federal do Rio Grande do Sul

The cellular basis of behavioral depression is poorly understood. Recent studies indicate that neurons in the lateral habenula (LHb) increase their activity when an animal receives a stimulus designed to produce disappointment. LHb neurons project to and inhibit dopamine-rich regions such as the ventral-tegmental area (VTA) and substantia nigra, which control reward-seeking behavior. Here we show in brain slices that excitatory synapses onto LHb neurons projecting to the VTA are dramatically potentiated in two rat models of depression. VTA-projecting neurons also fire more, independent of synaptic input. Inactivation of LHb, using a protocol that mimics the deep brain stimulation (DBS) for depressed patients, acutely reverses the depressive behaviors in rats. Thus, we propose that increased tonic and synaptically-evoked firing of LHb neurons inhibits dopamine regions, enhancing basal and event-triggered disappointment signals leading to reduced reward-seeking behavior; DBS of LHb improves the behavioral deficits, presumably by suppressing LHb output.