Hadjas Lotfi C., Lüscher Christian, Simmler Linda D. (2019), Aberrant habit formation in the Sapap3-knockout mouse model of obsessive-compulsive disorder, in Scientific Reports
, 9(1), 12061-12061.
Loureiro Michaël, Achargui Ridouane, Flakowski Jérôme, Van Zessen Ruud, Stefanelli Thomas, Pascoli Vincent, Lüscher Christian (2019), Social transmission of food safety depends on synaptic plasticity in the prefrontal cortex, in Science
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Nestler Eric J., Lüscher Christian (2019), The Molecular Basis of Drug Addiction: Linking Epigenetic to Synaptic and Circuit Mechanisms, in Neuron
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Pascoli Vincent, Hiver Agnès, Van Zessen Ruud, Loureiro Michaël, Achargui Ridouane, Harada Masaya, Flakowski Jérôme, Lüscher Christian (2018), Stochastic synaptic plasticity underlying compulsion in a model of addiction, in Nature
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CorreJulie, van ZessenRuud, LoureiroMichaël, PatriarchiTommaso, TianLin, PascoliVincent, LüscherChristian (2018), Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement, in eLife
Mendez Pablo, Stefanelli Thomas, Flores Carmen E., Muller Dominique, Lüscher Christian (2018), Homeostatic Plasticity in the Hippocampus Facilitates Memory Extinction, in Cell Reports
, 22(6), 1451-1461.
Lee Dongmin, Creed Meaghan, Jung Kanghoon, Stefanelli Thomas, Wendler Daniel J, Oh Won Chan, Mignocchi Neymi Layne, Lüscher Christian, Kwon Hyung-Bae (2017), Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain, in Nature Methods
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We hypothesize that addiction constitutes a syndrome of reinforcement and negative affect that is driven by drug-evoked plasticity at specific synapses in the mesolimbic dopamine system. Here we will focus on the ventral pallidum, which, according to our preliminary data, may constitute a hub integrating reinforcement and aversion. Identification and characterization of drug-evoked synaptic plasticity may enable to design stimulation protocols to restore normal transmission at identified synapses, which may erase specific adaptive behaviors, in the quest to establishing links of causalities. We will test this hypothesis by carrying out the following aims:1.We will characterize cocaine evoked synaptic plasticity in the VP, a downstream target of D1 and D2R expressing medium spiny neurons of the nucleus accumbens. 2. We will monitor behavioral sensitization and hedonic taste perception and motivation as adaptive behaviors reflecting incentive saliency and negative affect.3. We will establish reversal protocols to establish links of causality between changes in synaptic plasticity and drug-adaptive behavior. A successfully completion of the present project will constitute an important step forward in the establishment of a comprehensive circuit model of drug addiction, which will open the door for novel, rational therapeutic strategies, such as deep brain stimulation.