Dopamine-dependent prefrontal reactivations explain long-term benefit of fear extinction

Nat Commun. 2018 Oct 16;9(1):4294. doi: 10.1038/s41467-018-06785-y.

Abstract

Fear extinction does not prevent post-traumatic stress or have long-term therapeutic benefits in fear-related disorders unless extinction memories are easily retrieved at later encounters with the once-threatening stimulus. Previous research in rodents has pointed towards a role for spontaneous prefrontal activity occurring after extinction learning in stabilizing and consolidating extinction memories. In other memory domains spontaneous post-learning activity has been linked to dopamine. Here, we show that a neural activation pattern - evoked in the ventromedial prefrontal cortex (vmPFC) by the unexpected omission of the feared outcome during extinction learning - spontaneously reappears during postextinction rest. The number of spontaneous vmPFC pattern reactivations predicts extinction memory retrieval and vmPFC activation at test 24 h later. Critically, pharmacologically enhancing dopaminergic activity during extinction consolidation amplifies spontaneous vmPFC reactivations and correspondingly improves extinction memory retrieval at test. Hence, a spontaneous dopamine-dependent memory consolidation-based mechanism may underlie the long-term behavioral effects of fear extinction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Dopamine / administration & dosage
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Extinction, Psychological / physiology
  • Fear / physiology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory Consolidation
  • Nontherapeutic Human Experimentation
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*

Substances

  • Dopamine