Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization

Abstract

Cocaine-induced alterations in synaptic glutamate function in nucleus accumbens are thought to mediate drug-related behaviors such as psychomotor sensitization. However, previous studies 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 while the majority of accumbens neurons are less directly involved. Here, we assessed synaptic alterations in these strongly activated accumbens neurons in c-fos-GFP mice that express a fusion protein of Fos and green fluorescent protein (GFP) in strongly activated neurons and compared these alterations with those in surrounding non-activated neurons. Cocaine sensitization produced higher levels of ‘silent synapses’ that contained functional NMDA receptors and non-functional AMPA receptors in only GFP-positive neurons, 6–11 days after sensitization. Thus unique synaptic alterations are induced in the most strongly activated accumbens neurons that mediate psychomotor sensitization.