Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization

Nat Neurosci. 2012 Nov;15(11):1556-62. doi: 10.1038/nn.3232. Epub 2012 Sep 30.


Cocaine-induced alterations in synaptic glutamate function in nucleus accumbens are thought to mediate drug-related behaviors such as psychomotor sensitization. However, previous studies have examined global alterations in randomly selected accumbens neurons regardless of their activation state during cocaine-induced behavior. We recently found that a minority of strongly activated Fos-expressing accumbens neurons are necessary for cocaine-induced psychomotor sensitization, whereas the majority of accumbens neurons are less directly involved. We assessed synaptic alterations in these strongly activated accumbens neurons in Fos-GFP mice, which express a fusion protein of Fos and GFP in strongly activated neurons, and compared these alterations with those in surrounding non-activated neurons. Cocaine sensitization produced higher levels of 'silent synapses', which contained functional NMDA receptors and nonfunctional AMPA receptors only in GFP-positive neurons, 6-11 d after sensitization. Thus, distinct synaptic alterations are induced in the most strongly activated accumbens neurons that mediate psychomotor sensitization.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Analysis of Variance
  • Anesthetics, Local / pharmacology
  • Animals
  • Biophysics
  • Cocaine / metabolism
  • Cocaine / pharmacology*
  • Dopamine Uptake Inhibitors / metabolism
  • Dopamine Uptake Inhibitors / pharmacology*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / drug effects*
  • Nucleus Accumbens / cytology*
  • Patch-Clamp Techniques
  • Synapses / drug effects*
  • Synapses / physiology
  • Tetrodotoxin / pharmacology
  • Time Factors


  • Anesthetics, Local
  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • Green Fluorescent Proteins
  • Tetrodotoxin
  • 2-Amino-5-phosphonovalerate
  • Cocaine