Targeting the Ventral Pallidum to Treat Addictive Disorders
Jeudi 11 octobre 2018 11:30
- Duree : 1 heure
Lieu : Amphithéâtre Serge Kampf, Grenoble Institut des Neurosciences (GIN) - Bât. Edmond J. Safra, Chemin Fortune Ferrini CHU, La Tronche
Orateur : Meaghan CREED (University of Maryland School of Medicine, Baltimore, USA)
Addiction is a disorder of behavioral symptoms including sensitization to drug-associated cues, negative affect and compulsive drug seeking. Cocaine-evoked synaptic plasticity in the reward sys-tem, particularly the nucleus accumbens (NAc) and its main output structure, the ventral pallidum (VP) drives drug-adaptive behavior. However, how information is integrated downstream of the NAc remains unclear. Here, we identify the ventral pallidum (VP) as a site of convergence of direct and indirect pathways from the NAc. Cocaine potentiated output of D1-MSNs, but weakened output of D2-MSNs, occluding LTP and LTD at these synapses, respectively. Restoring basal transmission at D1-MSN-to-VP synapses abolished locomotor sensitization, whereas restoring transmission at D2-MSN-to-VP synapses normalized motivational deficits. We further identified a non-canonical population of neurons in the VP that specifically constrain reward seeking in the face of aversive consequences, which is a hallmark feature of addiction. Our results support a model by which drug-evoked synaptic plasticity in the VP mediates diverse behavioral symptoms of addiction ; targeting the VP with neuromodulation may provide novel therapeutic strategies for addictive disorders.
Contact : sabrina.boulet@univ-grenoble-alpes.fr
Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (GIN)
Nature évènement : (Séminaire)
Evènement répétitif : (Séminaire Grenoblois de Neurosciences)
Site de l'évènement : Pôle Santé / La Tronche
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