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 language | English (US) |
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Pages (from-to) | 1453-1467 |
Number of pages | 15 |
Journal | Neuron |
Volume | 83 |
Issue number | 6 |
DOIs | |
State | Published - 2014 |
Externally published | Yes |
ASJC Scopus subject areas
- General Neuroscience