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Locus coeruleus toggles reciprocal prefrontal firing to reinstate fear.

ABSTRACT: The medial prefrontal cortex (mPFC) plays an essential role in regulating emotion, including inhibiting fear when danger has passed. The extinction of fear, however, is labile and a number of factors, including stress, cause extinguished fear to relapse. Here we show that fear relapse in rats limits single-unit activity among infralimbic (IL) neurons, which are critical for inhibiting fear responses, and facilitates activity in prelimbic (PL) neurons involved in fear expression. Pharmacogenetic activation of noradrenergic neurons in the locus coeruleus mimics this shift in reciprocal IL-PL spike firing, increases the expression of conditioned freezing behavior, and causes relapse of extinguished fear. Noradrenergic modulation of mPFC firing represents a mechanism for relapse and a potential target for therapeutic interventions to reduce pathological fear.

SUBMITTER: Giustino TF

PROVIDER: S-EPMC6486780 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Locus coeruleus toggles reciprocal prefrontal firing to reinstate fear.

Giustino Thomas F TF Fitzgerald Paul J PJ Ressler Reed L RL Maren Stephen S

Proceedings of the National Academy of Sciences of the United States of America 20190410 17

The medial prefrontal cortex (mPFC) plays an essential role in regulating emotion, including inhibiting fear when danger has passed. The extinction of fear, however, is labile and a number of factors, including stress, cause extinguished fear to relapse. Here we show that fear relapse in rats limits single-unit activity among infralimbic (IL) neurons, which are critical for inhibiting fear responses, and facilitates activity in prelimbic (PL) neurons involved in fear expression. Pharmacogenetic ...[more]

PMID: 30971490

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