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Nat Neurosci. 2012 Nov;15(11):1556-62. doi: 10.1038/nn.3232. Epub 2012 Sep 30.

Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization.

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  • 1Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, US National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland, USA.


Cocaine-induced alterations in synaptic glutamate function in nucleus accumbens are thought to mediate drug-related behaviors such as psychomotor sensitization. However, previous studies have examined global alterations in randomly selected accumbens neurons regardless of their activation state during cocaine-induced behavior. We recently found that a minority of strongly activated Fos-expressing accumbens neurons are necessary for cocaine-induced psychomotor sensitization, whereas the majority of accumbens neurons are less directly involved. We assessed synaptic alterations in these strongly activated accumbens neurons in Fos-GFP mice, which express a fusion protein of Fos and GFP in strongly activated neurons, and compared these alterations with those in surrounding non-activated neurons. Cocaine sensitization produced higher levels of 'silent synapses', which contained functional NMDA receptors and nonfunctional AMPA receptors only in GFP-positive neurons, 6-11 d after sensitization. Thus, distinct synaptic alterations are induced in the most strongly activated accumbens neurons that mediate psychomotor sensitization.

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