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 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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Acknowledgements
We thank A. Barth for providing the first line of Fos-GFP mice, K. Knestaut and J. Hug for breeding the Fos-GFP mice, and E. Goldart and R. Ator for genotyping assistance. We thank S. Hall and T. Shippenberg for the use of their locomotor activity chambers. We thank S. Kourrich for many fruitful discussions regarding synaptic plasticity in the nucleus accumbens. This research was supported by the National Institute on Drug Abuse, Intramural Research Program.
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E.K., F.C.C. and B.T.H. designed the behavioral experiments. E.K. performed these experiments with F.C.C., R.A., S.A.G. and B.T.H. E.K., A.F.H. and C.R.L. designed the electrophysiology experiments. C.R.L. designed and built the spinning disc confocal and electrophysiology apparatuses. E.K. conducted and analyzed the data from the behavior, immunohistochemistry and electrophysiology experiments. E.K., B.T.H. and C.R.L. wrote the paper.
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Koya, E., Cruz, F., Ator, R. et al. Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization. Nat Neurosci 15, 1556–1562 (2012). https://doi.org/10.1038/nn.3232
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DOI: https://doi.org/10.1038/nn.3232
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