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Proc Natl Acad Sci U S A. 2019 Apr 10. pii: 201814278. doi: 10.1073/pnas.1814278116. [Epub ahead of print]

Locus coeruleus toggles reciprocal prefrontal firing to reinstate fear.

Author information

1
Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843-4235.
2
Institute for Neuroscience, Texas A&M University, College Station, TX 77843-3474.
3
Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843-4235; maren@tamu.edu.

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.

KEYWORDS:

extinction; locus coeruleus; norepinephrine; prefrontal cortex; relapse

PMID:
30971490
DOI:
10.1073/pnas.1814278116
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Conflict of interest statement

The authors declare no conflict of interest.

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