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

A. M. V. Gerlicher (), O. Tüscher and R. Kalisch
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A. M. V. Gerlicher: Johannes Gutenberg University Medical Center
O. Tüscher: Johannes Gutenberg University Medical Center
R. Kalisch: Johannes Gutenberg University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06785-y

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