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Séminaire - Jacques BarikExcitatory inputs to VTA dopamine neurons regulate depressive-like behaviors

Abstract :

Depression is a major human blight with more than 350 million people affected worldwide. Yet, curative treatments are lacking due to our still very limited understanding of its pathophysiology. Long-lasting periods of stress as well as traumatic stressful experiences trigger molecular and cellular maladaptations that affect emotional and social behaviors. Hence, stress is a primary environmental factor that is acknowledged as a key element in the developmental root of a large part of mental disorders including depression and thus a leading cause of disability worldwide. Dysregulation of dopamine (DA) neurons from the ventral tegmental area (VTA) has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, little is known about the relevant inputs that regulate the changes in activity of VTA DA neurons that are responsible for the appearance of these behavioral maladaptations. Here, we exposed mice to chronic social defeat stress (CSD), a preclinical paradigm of depression. We combined ex-vivo patch recordings in genetically-tagged neuronal cell types to dissect the impact of social stress on excitatory inputs to the VTA. We used chemogenetic and pharmacological approaches to causally link these cellular changes to the appearance of social withdrawal and anhedonia. Our data indicate that mesopontine excitatory inputs to the VTA are essential to promote depressive-like behaviors. This work will favor the development of circuitbased interventions to alleviate symptoms of depression

Scientific focus :

Jacques BARIK

Après une thèse en neurosciences en Angleterre et un postdoctorat au Collège de France, Jacques Barik a rejoint l’Université Pierre et Marie Curie en 2010.

Depuis septembre 2013, il est au sein de l’université de Nice et co-dirige avec le Dr Hélène Marie une équipe de recherche à l’Institut de Pharmacologie Moléculaire et Cellulaire (Sophia Antipolis, Valbonne). Ses travaux de recherche portent sur l’impact de facteurs environnementaux tels que le stress et les drogues d’abus sur le cerveau. Il s’intéresse, en particulier, aux adaptations cellulaires induites au sein du système dit de récompense et leurs répercussions sur le comportement de l’animal.