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

Kenneth M. McCullough, Chris Chatzinakos, Jakob Hartmann, Galen Missig, Rachael L. Neve, Robert J. Fenster, William A. Carlezon, Nikolaos P. Daskalakis () and Kerry J. Ressler ()
Additional contact information
Kenneth M. McCullough: McLean Hospital, Department of Psychiatry, Harvard Medical School
Chris Chatzinakos: McLean Hospital, Department of Psychiatry, Harvard Medical School
Jakob Hartmann: McLean Hospital, Department of Psychiatry, Harvard Medical School
Galen Missig: McLean Hospital, Department of Psychiatry, Harvard Medical School
Rachael L. Neve: Gene Transfer Core, Massachusetts General Hospital
Robert J. Fenster: McLean Hospital, Department of Psychiatry, Harvard Medical School
William A. Carlezon: McLean Hospital, Department of Psychiatry, Harvard Medical School
Nikolaos P. Daskalakis: McLean Hospital, Department of Psychiatry, Harvard Medical School
Kerry J. Ressler: McLean Hospital, Department of Psychiatry, Harvard Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18985-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18985-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18985-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().