1. Differential fear conditioning generates prefrontal neural ensembles of safety signals.
- Author
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Corches A, Hiroto A, Bailey TW, Speigel JH 3rd, Pastore J, Mayford M, and Korzus E
- Subjects
- AIDS-Related Complex genetics, AIDS-Related Complex metabolism, Analysis of Variance, Animals, Doxycycline pharmacology, Freezing Reaction, Cataleptic physiology, Gene Expression drug effects, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Histones genetics, Histones metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Phosphopyruvate Hydratase metabolism, Time Factors, Conditioning, Classical physiology, Discrimination, Psychological physiology, Fear physiology, Neurons physiology, Prefrontal Cortex cytology
- Abstract
Fear discrimination is critical for survival, while fear generalization is effective for avoiding dangerous situations. Overgeneralized fear is a typical symptom of anxiety disorders, including generalized anxiety disorder and posttraumatic stress disorder (PTSD). Previous research demonstrated that fear discrimination learning is mediated by prefrontal mechanisms. While the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) are recognized for their excitatory and inhibitory effects on the fear circuit, respectively, the mechanisms driving fear discrimination are unidentified. To obtain insight into the mechanisms underlying context-specific fear discrimination, we investigated prefrontal neuronal ensembles representing distinct experiences associated with learning to disambiguate between dangerous and similar, but not identical, harmless stimuli. Here, we show distinct quantitative activation differences in response to conditioned and generalized fear experiences, as well as modulation of the neuronal ensembles associated with successful acquisition of context-safety contingencies. These findings suggest that prefrontal neuronal ensembles patterns code functional context-danger and context-safety relationships. The PL subdivision of the mPFC monitors context-danger associations to conditioned fear, whereas differential conditioning sparks additional ensembles associated with the inhibition of generalized fear in both the PL and IL subdivisions of the mPFC. Our data suggest that fear discrimination learning is associated with the modulation of prefrontal subpopulations in a subregion- and experience-specific fashion, and the learning of appropriate responses to conditioned and initially generalized fear experiences is driven by gradual updating and rebalancing of the prefrontal memory representations., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
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