A transient but prominent increase in the level of “silent synapses”—a signature of immature glutamatergic synapses that contain only NMDA receptors without stably expressed AMPA receptors—has been identified in the nucleus accumbens (NAc) following exposure to cocaine. As the NAc is a critical forebrain region implicated in forming addiction-associated behaviors, the initial discoveries have raised speculations about whether and how these drug-induced synapses mature and potentially contribute to addiction-related behaviors. Here, we summarize recent progress in recognizing the pathway-specific regulations of silent synapse maturation, and its diverse impacts on behavior. We provide an update of the guiding hypothesis—the “neural rejuvenation hypothesis”—with recently emerged evidence of silent synapses in cocaine craving and relapse.
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