Objectif The mesocorticolimbic (MCL) system, extending from the ventral tegmental area (VTA) to the nucleus accumbens and prefrontal cortex, comprises a dopamine (DA) projection implicated in reinforcement learning. The MCL system is the target of addictive substances and of drug-evoked synaptic plasticity, a cellular mechanism that may underlie the adaptive, pathological behaviors that occur after repeated drug exposure. While most previous work has focused on excitatory transmission, recent studies suggest that inhibitory transmission may play a crucial role in mediating specific functions of the MCL system. However the identity of the inhibitory synapses and circuits and the plasticity mechanisms underlying these forms of normal and pathological learning remain elusive. We hypothesize that distinct inhibitory circuits in the MCL system mediate specific behaviors and that adaptive synaptic plasticity of these circuits are fundamental to both normal reward learning and addictive behaviors.We will test this hypothesis using optogenetic projection targeting to characterize specific inhibitory projections, to selectively change the activity of these neurons in freely behaving animals to explore their behavioral relevance, and to identify precise circuit changes that underlie behavioral alterations after drug exposure. Taken together, the experiments we propose will not only identify the specific circuits and basic role of inhibition in mediating reward-related behaviors, but will allow us to understand how the alteration of these circuits after drugs can result in pathological behavior. Ultimately, our results will establish the importance of inhibitory synaptic transmission in the MCL system, are likely to fundamentally change current views of this important modulatory system, and will allow us to design strategies to interfere with drug-evoked synaptic plasticity to revert addictive behavior. Champ scientifique natural sciencescomputer and information sciencesartificial intelligencemachine learningreinforcement learning Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Appel à propositions ERC-2012-ADG_20120314 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil UNIVERSITE DE GENEVE Contribution de l’UE € 2 499 506,00 Adresse RUE DU GENERAL DUFOUR 24 1211 Geneve Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Genève Type d’activité Higher or Secondary Education Establishments Contact administratif Alex Waehry (Dr.) Chercheur principal Christian Lüscher (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITE DE GENEVE Suisse Contribution de l’UE € 2 499 506,00 Adresse RUE DU GENERAL DUFOUR 24 1211 Geneve Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Genève Type d’activité Higher or Secondary Education Establishments Contact administratif Alex Waehry (Dr.) Chercheur principal Christian Lüscher (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
