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Manuel Mameli"Drug-related memories: a synaptic perspective"

Abstract :


Goal directed actions, aimed to obtain a reward, motivate our behaviors and influence our decisions.
Midbrain dopamine neurons activity and therefore dopamine release are enhanced by external cues predicting a reward and at the same time are a principal target of addictive substances. A clear understanding on the neural circuits implicated in the effects of drugs partcicularly controlling dopamine neurons activity remains still elusive. Neurons in the lateral habenula (LHb) play a central role in tuning dopamine neurons activity during reward learning.  Addictive subtances induce an abnormal increase in dopamine neurons and recent theories posit that addiction develops by hijacking the reward system promoting strong association between drug and context. We combined in vitro electrophysiology, 2-photon laser photolysis and retrograde tracing to probe drug-evoked synaptic adaptation in key regions of the the reward circuit including the ventral tegmental area and the LHb. We have evidences that psychostimulants such as cocaine drastically alters the synaptic properties of excitatory inputs onto these neurons and their ability to undergo long-term plasticity providing a cellular mechanisms implicated during drug-seeking and drug-context association.

Selected publications

Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area.Mameli M, Bellone C, Brown MT, Lüscher C.Nat Neurosci. 2011 Apr;14(4):414-6. Epub 2011 Feb 20.

Synaptic plasticity and addiction: Learning mechanisms gone awry.Mameli M, Lüscher C.Neuropharmacology. 2011 Jan 28. [Epub ahead of print]

Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation.Brown MT, Bellone C, Mameli M, Labouèbe G, Bocklisch C, Balland B, Dahan L, Luján R, Deisseroth K, Lüscher C.PLoS One. 2010 Dec 31;5(12):e15870.

François Georges de l'IINS