Distinct hippocampal engrams control extinction and relapse of fear memory

Learned fear often relapses after extinction, suggesting that extinction training generates a new memory that coexists with the original fear memory; however, the mechanisms governing the expression of competing fear and extinction memories remain unclear. We used activity-dependent neural tagging t...

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Bibliographic Details
Published in:Nature neuroscience 2019-05, Vol.22 (5), p.753-761
Main Authors: Lacagnina, Anthony F, Brockway, Emma T, Crovetti, Chelsea R, Shue, Francis, McCarty, Meredith J, Sattler, Kevin P, Lim, Sean C, Santos, Sofia Leal, Denny, Christine A, Drew, Michael R
Format: Article
Language:English
Subjects:
Activation
Analysis
Animals
Biodiversity conservation
Brain
Conditioning, Classical - physiology
Dentate gyrus
Dentate Gyrus - physiology
Extinction (Learning)
Extinction (Psychology)
Extinction, Psychological - physiology
Fear
Fear - physiology
Fear conditioning
Female
Hippocampus
Male
Memory
Memory - physiology
Mental Recall - physiology
Mice, Transgenic
Neurons
Neurons - physiology
Neurosciences
Optogenetics
Psychological aspects
Recovery
Recurrence (Disease)
Representations
Spontaneous recovery
Stimulation
Training
Variance analysis
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Summary:Learned fear often relapses after extinction, suggesting that extinction training generates a new memory that coexists with the original fear memory; however, the mechanisms governing the expression of competing fear and extinction memories remain unclear. We used activity-dependent neural tagging to investigate representations of fear and extinction memories in the dentate gyrus. We demonstrate that extinction training suppresses reactivation of contextual fear engram cells while activating a second ensemble, a putative extinction engram. Optogenetic inhibition of neurons that were active during extinction training increased fear after extinction training, whereas silencing neurons that were active during fear training reduced spontaneous recovery of fear. Optogenetic stimulation of fear acquisition neurons increased fear, while stimulation of extinction neurons suppressed fear and prevented spontaneous recovery. Our results indicate that the hippocampus generates a fear extinction representation and that interactions between hippocampal fear and extinction representations govern the suppression and relapse of fear after extinction.
ISSN:1097-6256
1546-1726
DOI:10.1038/s41593-019-0361-z