CONICET | Buscador de Institutos y Recursos Humanos

Depression is a major human blight with more than350 million people affected worldwide. Yet, curative treatments are lacking dueto our still very limited understanding of its pathophysiology. Long-lastingperiods of stress as well as traumatic stressful experiences trigger molecularand cellular maladaptations that affect emotional and social behaviors. Hence,stress is a primary environmental factor that is acknowledged as a key elementin the developmental root of a large part of mental disorders includingdepression and thus a leading cause of disability worldwide. Dysregulation ofdopamine (DA) neurons from the ventral tegmental area (VTA) has been causallylinked to the appearance of social withdrawal and anhedonia, two classicalmanifestations of depression. However, little is known about the relevantinputs that regulate the changes in activity of VTA DA neurons that areresponsible for the appearance of these behavioral maladaptations. Here, weexposed mice to chronic social defeat stress (CSD), a preclinical paradigm ofdepression. We combined ex-vivo patch recordings in genetically-tagged neuronalcell types to dissect the impact of social stress on excitatory inputs to theVTA. To causally link these cellular changes to the appearance of socialwithdrawal and anhedonia we used chemogenetic approaches. This work will favorthe development of circuit-based interventions to alleviate symptoms ofdepression.