Silent Synapses Speak Up: Updates of the Neural Rejuvenation Hypothesis of Drug Addiction

Neuroscientist. 2015 Oct;21(5):451-9. doi: 10.1177/1073858415579405. Epub 2015 Mar 31.

Abstract

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.

Keywords: NMDA receptor; accumbens; addiction; cocaine; silent synapse; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cocaine* / administration & dosage
  • Humans
  • Neuronal Plasticity / drug effects*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rejuvenation / physiology*
  • Substance-Related Disorders / etiology*
  • Synapses / physiology*

Substances

  • Cocaine