Abstract: Avani SHUKLA

Fate of slient synapses in cocaine addiction

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Avani Shukla (1, 2), Anna Suska (1), Oliver M. Schlüter (1)

(1) European Neuroscience Institute-Göttingen, Germany
(2) International Max Planck Reseach School (IMPRS) for Molecular Biology, Göttingen

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Drugs of abuse such as cocaine, hijack synaptic plasticity mechanisms of the brain circuits controlling motivated behavior. The mesocorticolimbic dopamine system is the reward circuitry involved in positive reinforcement learning. A characteristic mechanism of drugs of abuse is to elevate dopamine levels in the nucleus accumbens (NAc). It has been shown recently that cocaine induces the generation of silent synapses in the NAc (Huang, Neuron 2009, Brown, J. Neurosci. 2011). Silent synapses contain NMDA receptors but lack AMPA receptors; therefore they do not transmit at resting potential and could hence serve as potential plasticity substrates for long-term potentiation. We aim to identify the role of these silent synapses in long-term retention of drug-associated behaviors. During long-term withdrawal from cocaine, GluA2-lacking calcium permeable AMPA receptors (CP-AMPARs) are induced in drug-related networks, which are considered to be an important signature of drug-related behavior. Do these CP-AMPARs originate from the cocaine-induced silent synapses? To address this question we have performed in mice, conditioned place preference (CPP) - a behavioral assay to test positive association with drug experience, followed by ex-vivo electrophysiology in NAc slices to measure the time course of generation of silent synapses and increase of CP-AMPARs during withdrawal from systemic cocaine injections. Our results suggest a conversion of silent synapses induced by repeated cocaine exposure, to CP-AMPAR containing synapses which are then consolidated into drug-induced synaptic connections in the NAc neuronal network to mediate drug-related behavior.