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

First Author  McCullough KM Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  5180
PubMed ID  33057013 Mgi Jnum  J:297626
Mgi Id  MGI:6471400 Doi  10.1038/s41467-020-18985-6
Citation  McCullough KM, et al. (2020) Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning. Nat Commun 11(1):5180
abstractText  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.
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