Format

Send to

Choose Destination
Nat Neurosci. 2013 Nov;16(11):1644-51. doi: 10.1038/nn.3533. Epub 2013 Sep 29.

Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving.

Author information

1
1] Department of Molecular Therapeutics, Scripps Research Institute, Jupiter, Florida, USA. [2] Program in Neuroscience, Washington State University, Pullman, Washington, USA. [3].

Abstract

In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after withdrawal from the drug. This 'incubation of cocaine craving' is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens (NAc). However, the circuit-level adaptations mediating this plasticity remain elusive. We studied silent synapses, often regarded as immature synapses that express stable NMDA receptors with AMPA receptors being either absent or labile, in the projection from the basolateral amygdala to the NAc in incubation of cocaine craving. Silent synapses were detected in this projection during early withdrawal from cocaine. As the withdrawal period progressed, these silent synapses became unsilenced, a process that involved synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs). In vivo optogenetic stimulation-induced downregulation of CP-AMPARs at amygdala-to-NAc synapses, which re-silenced some of the previously silent synapses after prolonged withdrawal, decreased incubation of cocaine craving. Our findings indicate that silent synapse-based reorganization of the amygdala-to-NAc projection is critical for persistent cocaine craving and relapse after withdrawal.

PMID:
24077564
PMCID:
PMC3815713
DOI:
10.1038/nn.3533
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center