Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections

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, Yan Dong

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Glutamatergic 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 1day of withdrawal. After 45days 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.

Original languageEnglish (US)
Pages (from-to)1453-1467
Number of pages15
JournalNeuron
Volume83
Issue number6
DOIs
StatePublished - Jan 1 2014

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ma, Y. Y., Lee, B. R., Wang, X., Guo, C., Liu, L., Cui, R., Lan, Y., Balcita-Pedicino, J. J., Wolf, M. E., Sesack, S. R., Shaham, Y., Schlüter, O. M., Huang, Y. H., & Dong, Y. (2014). Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections. Neuron, 83(6), 1453-1467. https://doi.org/10.1016/j.neuron.2014.08.023