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Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning

Citation:
Nature Communications 2020; 11: 5180. https://doi.org/10.1038/s41467-020-18985-6
Authored By:
McCullough, K.M., Chatzinakos, C., Hartmann, J. Galen Missig, Rachael L. Neve, Robert J. Fenster, William A. Carlezon Jr., Nikolaos P. Daskalakis & Kerry J. Ressler
Abstract:
Fear and extinction learning are adaptive processes caused by molecular changes in specific neural circuits. Neurons expressing the corticotropin-releasing hormone gene (Crh) in central amygdala (CeA) are implicated in threat regulation, yet little is known of cell type-specific gene pathways mediating adaptive learning. We translationally profiled the transcriptome of CeA Crh-expressing cells (Crh neurons) after fear conditioning or extinction in mice using translating ribosome affinity purification (TRAP) and RNAseq. Differential gene expression and co-expression network analyses identified diverse networks activated or inhibited by fear vs extinction. Upstream regulator analysis demonstrated that extinction associates with reduced CREB expression, and viral vector-induced increased CREB expression in Crh neurons increased fear expression and inhibited extinction. These findings suggest that CREB, within CeA Crh neurons, may function as a molecular switch that regulates expression of fear and its extinction. Cell-type specific translational analyses may suggest targets useful for understanding and treating stress-related psychiatric illness.
Published in:
Nature Communications

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