Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction

Nat Commun. 2020 Aug 31;11(1):4358. doi: 10.1038/s41467-020-18199-w.


Learned fear and safety are associated with distinct oscillatory states in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). To determine if and how these network states support the retrieval of competing memories, we mimicked endogenous oscillatory activity through optogenetic stimulation of parvalbumin-expressing interneurons in mice during retrieval of contextual fear and extinction memories. We found that exogenously induced 4 Hz and 8 Hz oscillatory activity in the BLA exerts bi-directional control over conditioned freezing behavior in an experience- and context-specific manner, and that these oscillations have an experience-dependent ability to recruit distinct functional neuronal ensembles. At the network level we demonstrate, via simultaneous manipulation of BLA and mPFC, that experience-dependent 4 Hz resonance across BLA-mPFC circuitry supports post-extinction fear memory retrieval. Our findings reveal that post-extinction fear memory retrieval is supported by local and interregional experience-dependent resonance, and suggest novel approaches for interrogation and therapeutic manipulation of acquired fear circuitry.

Publication types

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

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Basolateral Nuclear Complex / physiology
  • Conditioning, Psychological
  • Electrophysiology / methods
  • Extinction, Psychological*
  • Fear / physiology*
  • Learning / physiology
  • Memory / physiology*
  • Mice
  • Optogenetics / methods
  • Prefrontal Cortex / physiology