Amygdala Reward Neurons Form and Store Fear Extinction Memory

Neuron. 2020 Mar 18;105(6):1077-1093.e7. doi: 10.1016/j.neuron.2019.12.025. Epub 2020 Jan 14.

Abstract

The ability to extinguish conditioned fear memory is critical for adaptive control of fear response, and its impairment is a hallmark of emotional disorders like post-traumatic stress disorder (PTSD). Fear extinction is thought to take place when animals form a new memory that suppresses the original fear memory. However, little is known about the nature and the site of formation and storage of this new extinction memory. Here we demonstrate that a fear extinction memory engram is formed and stored in a genetically distinct basolateral amygdala (BLA) neuronal population that drives reward behaviors and antagonizes the BLA's original fear neurons. Activation of fear extinction engram neurons and natural reward-responsive neurons overlap significantly in the BLA. Furthermore, these two neuronal subsets are mutually interchangeable in driving reward behaviors and fear extinction behaviors. Thus, fear extinction memory is a newly formed reward memory. VIDEO ABSTRACT.

Keywords: PTSD; amygdala; engram; fear extinction; fear memory; memory; neural circuits; reward; valence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Conditioning, Psychological / physiology
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism
  • Neurons / physiology*
  • Optogenetics
  • Reward*

Substances

  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Ppp1r1b protein, mouse