Depressed rats display potentiated excitatory synapse and increased firing at neurons that provide disappointment signals

B. LI, J. PIRIZ, M. MIRRIONE, D. SCHULZ, F. HENN, R. MALINOW

Chicago

Congreso; Annual Meeting of the Society for Neuroscience; 2009

Society for Neuroscience

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.