Silent synapses dictate cocaine memory destabilization and reconsolidation

William J. Wright, Nicholas M. Graziane, Peter A. Neumann, Peter J. Hamilton, Hannah M. Cates, Lauren Fuerst, Alexander Spenceley, Natalie MacKinnon-Booth, Kartik Iyer, Yanhua H. Huang, Yavin Shaham, Oliver M. Schlüter, Eric J. Nestler, Yan Dong

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Cocaine-associated memories are persistent, but, on retrieval, become temporarily destabilized and vulnerable to disruptions, followed by reconsolidation. To explore the synaptic underpinnings for these memory dynamics, we studied AMPA receptor (AMPAR)-silent excitatory synapses, which are generated in the nucleus accumbens by cocaine self-administration, and subsequently mature after prolonged withdrawal by recruiting AMPARs, echoing acquisition and consolidation of cocaine memories. We show that, on memory retrieval after prolonged withdrawal, the matured silent synapses become AMPAR-silent again, followed by re-maturation ~6 h later, defining the onset and termination of a destabilization window of cocaine memories. These synaptic dynamics are timed by Rac1, with decreased and increased Rac1 activities opening and closing, respectively, the silent synapse-mediated destabilization window. Preventing silent synapse re-maturation within the destabilization window decreases cue-induced cocaine seeking. Thus, cocaine-generated silent synapses constitute a discrete synaptic ensemble dictating the dynamics of cocaine-associated memories and can be targeted for memory disruption.

Original languageEnglish (US)
Pages (from-to)32-46
Number of pages15
JournalNature Neuroscience
Issue number1
StatePublished - Jan 1 2020

All Science Journal Classification (ASJC) codes

  • General Neuroscience


Dive into the research topics of 'Silent synapses dictate cocaine memory destabilization and reconsolidation'. Together they form a unique fingerprint.

Cite this