Publication

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

More Publications

May 19, 2023

Nature Reviews Neurology

Global synergistic actions to improve brain health for human development

April 20, 2023

Nature Mental Health

Machine learning-based identification of a psychotherapy-predictive electroencephalographic signature in PTSD

February 13, 2023

Frontiers in Aging Neuroscience

Machine learning within the Parkinson’s progression markers initiative: Review of the current state of affairs

September 9, 2022

Sensors

Deep Learning for Daily Monitoring of Parkinson’s Disease Outside the Clinic Using Wearable Sensors

June 1, 2022

JAMA Network Open

Association of Posttraumatic Stress Disorder With Accelerated Cognitive Decline in Middle-aged Women

March 23, 2022

Journal of Neurotrauma

A Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury