• Yao-Ying Ma, Brian R Lee, Xiusong Wang, Changyong Guo, Lei Liu, Ranji Cui, Yan Lan, Judith J Balcita-Pedicino, Marina E Wolf, Susan R Sesack, Yavin Shaham, Oliver M Schlüter, Yanhua H Huang, and Yan Dong.
• Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
• Neuron. 2014 Sep 17;83(6):1453-67.

AbstractGlutamatergic projections from the medial prefrontal cortex (mPFC) to nucleus accumbens (NAc) contribute to cocaine relapse. Here we show that silent synapse-based remodeling of the two major mPFC-to-NAc projections differentially regulated the progressive increase in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Specifically, cocaine self-administration in rats generated AMPA receptor-silent glutamatergic synapses within both infralimbic (IL) and prelimbic mPFC (PrL) to NAc projections, measured after 1 day of withdrawal. After 45 days of withdrawal, IL-to-NAc silent synapses became unsilenced/matured by recruiting calcium-permeable (CP) AMPARs, whereas PrL-to-NAc silent synapses matured by recruiting non-CP-AMPARs, resulting in differential remodeling of these projections. Optogenetic reversal of silent synapse-based remodeling of IL-to-NAc and PrL-to-NAc projections potentiated and inhibited, respectively, incubation of cocaine craving on withdrawal day 45. Thus, pro- and antirelapse circuitry remodeling is induced in parallel after cocaine self-administration. These results may provide substrates for utilizing endogenous antirelapse mechanisms to reduce cocaine relapse.Copyright © 2014 Elsevier Inc. All rights reserved.

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