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

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 aft...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Vol. 83; no. 6; p. 1453
Main Authors: Ma, Yao-Ying, Lee, Brian R, Wang, Xiusong, Guo, Changyong, Liu, Lei, Cui, Ranji, Lan, Yan, Balcita-Pedicino, Judith J, Wolf, Marina E, Sesack, Susan R, Shaham, Yavin, Schlüter, Oliver M, Huang, Yanhua H, Dong, Yan
Format: Journal Article
Language:English
Published: United States 17.09.2014
Subjects:
Animals
Cocaine-Related Disorders - physiopathology
Craving - physiology
Drug-Seeking Behavior - physiology
Electrophysiology
Male
Neural Pathways - drug effects
Neural Pathways - physiopathology
Neuronal Plasticity - physiology
Nucleus Accumbens - drug effects
Nucleus Accumbens - physiopathology
Optogenetics
Prefrontal Cortex - drug effects
Prefrontal Cortex - physiopathology
Rats
Rats, Sprague-Dawley
Synapses - drug effects
Synapses - physiology
ISSN:1097-4199, 1097-4199
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Summary: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.
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ISSN:1097-4199
1097-4199
DOI:10.1016/j.neuron.2014.08.023