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

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

Author information

1
Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany. a.m.v.gerlicher@uva.nl.
2
Deutsches Resilienz Zentrum (DRZ), Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany. a.m.v.gerlicher@uva.nl.
3
Department of Clinical Psychology, University of Amsterdam, Nieuwe Achtergracht 129B, 1018 WS, Amsterdam, The Netherlands. a.m.v.gerlicher@uva.nl.
4
Deutsches Resilienz Zentrum (DRZ), Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
5
Department of Psychiatry and Psychotherapy, Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
6
Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.

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.

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