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Neuron. 2014 Sep 17;83(6):1453-67. doi: 10.1016/j.neuron.2014.08.023. Epub 2014 Sep 4.

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

Author information

1
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
2
Allen Institute for Brain Science, Seattle, WA 98103, USA.
3
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
4
School of Life Science, Northeastern Normal University, Jilin, China.
5
Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
6
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
7
Behavioral Neuroscience Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD 21224, USA.
8
Molecular Neurobiology and Cluster of Excellence "Nanoscale Microscopy and Molecular Physiology of the Brain," European Neuroscience Institute, 37077 Göttingen, Germany.
9
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: huangy3@upmc.edu.
10
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: yandong@pitt.edu.

Erratum in

  • Neuron. 2014 Dec 17;84(6):1344-5.

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 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.

PMID:
25199705
PMCID:
PMC4295617
DOI:
10.1016/j.neuron.2014.08.023
[Indexed for MEDLINE]
Free PMC Article

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