Figure 1.

Cocaine-induced generation of silent synapses in the NAc. A, Schematic depiction of synaptogenesis in an MSN within the NAc during and following cocaine self-administration. During self-administration training, nascent, immature synapses are generated along the dendritic arbor, forming new connections. During withdrawal, some of these synapses mature into functional synapses, whereas others are presumably pruned away. Numbers correspond to the stages depicted in B. B, Illustration of the stages of cocaine-induced synapse generation and maturation. During cocaine self-administration, synaptogenic processes are triggered. This leads to the generation of new synapses, which contain both GluN2B-containing NMDARs and GluA2-containing AMPARs. These AMPARs, however, are highly labile and are soon internalized, resulting in silent synapses containing only NMDARs. During early withdrawal, GluN2B-containing NMDARs are replaced with GluN2A-containing NMDARs. This is critical for the subsequent functional maturation of the synapse mediated by the recruitment of CP-AMPARs to the synapse.