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Calcium‐permeable AMPA receptors and silent synapses in cocaine‐conditioned place preference
Author(s) -
Shukla Avani,
Beroun Anna,
Panopoulou Myrto,
Neumann Peter A,
Grant Seth GN,
Olive M Foster,
Dong Yan,
Schlüter Oliver M
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695465
Subject(s) - ampa receptor , biology , calcium , conditioned place preference , silent synapse , receptor , neuroscience , microbiology and biotechnology , nmda receptor , biophysics , biochemistry , medicine
Exposure to cocaine generates silent synapses in the nucleus accumbens ( NA c), whose eventual unsilencing/maturation by recruitment of calcium‐permeable AMPA ‐type glutamate receptors ( CP ‐ AMPAR s) after drug withdrawal results in profound remodeling of NA c neuro‐circuits. Silent synapse‐based NA c remodeling was shown to be critical for several drug‐induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug‐associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD ‐93, PSD ‐95, and SAP 102 differentially regulate excitatory synapse properties in the NA c. Mice deficient for either of these scaffold proteins exhibit distinct maturation patterns of silent synapses and thus provided instructive animal models to examine the role of NA c silent synapse maturation in cocaine‐conditioned place preference ( CPP ). Wild‐type and knockout mice alike all acquired cocaine‐ CPP and exhibited increased levels of silent synapses after drug‐context conditioning. However, the mice differed in CPP retention and CP ‐ AMPAR incorporation. Collectively, our results indicate that CP ‐ AMPAR ‐mediated maturation of silent synapses in the NA c is a signature of drug–context association, but this maturation is not required for establishing or retaining cocaine‐ CPP .