Cellular and oscillatory substrates of fear extinction learning

Nat Neurosci. 2017 Nov;20(11):1624-1633. doi: 10.1038/nn.4651. Epub 2017 Oct 2.


The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6-12 Hz oscillation and a fear-associated 3-6 Hz oscillation within the BLA. Loss of this competition increases a 3-6 Hz oscillatory signature, with BLA→medial prefrontal cortex directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

MeSH terms

  • Animals
  • Basolateral Nuclear Complex / cytology
  • Basolateral Nuclear Complex / physiology*
  • Biological Clocks / physiology*
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Fear / psychology
  • Female
  • Learning / physiology*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Transgenic
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*