Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses

Neuron. 2013 Nov 20;80(4):1054-65. doi: 10.1016/j.neuron.2013.07.047. Epub 2013 Oct 31.


A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit.

Publication types

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

MeSH terms

  • Amygdala / physiology
  • Animals
  • Behavior, Animal / physiology
  • Cholecystokinin / metabolism
  • Electroshock
  • Extinction, Psychological / physiology*
  • Fear / psychology*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Interneurons / physiology
  • Learning / physiology
  • Limbic System / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neural Pathways / physiology
  • Neurons / physiology
  • Parvalbumins / metabolism
  • Proto-Oncogene Proteins c-fos / physiology
  • Receptor, Cannabinoid, CB1 / metabolism
  • Synapses / physiology*


  • Parvalbumins
  • Proto-Oncogene Proteins c-fos
  • Receptor, Cannabinoid, CB1
  • Cholecystokinin