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Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning
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 mediat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560654/ https://www.ncbi.nlm.nih.gov/pubmed/33057013 http://dx.doi.org/10.1038/s41467-020-18985-6 |
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author | McCullough, Kenneth M. Chatzinakos, Chris Hartmann, Jakob Missig, Galen Neve, Rachael L. Fenster, Robert J. Carlezon, William A. Daskalakis, Nikolaos P. Ressler, Kerry J. |
author_facet | McCullough, Kenneth M. Chatzinakos, Chris Hartmann, Jakob Missig, Galen Neve, Rachael L. Fenster, Robert J. Carlezon, William A. Daskalakis, Nikolaos P. Ressler, Kerry J. |
author_sort | McCullough, Kenneth M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7560654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75606542020-10-19 Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning McCullough, Kenneth M. Chatzinakos, Chris Hartmann, Jakob Missig, Galen Neve, Rachael L. Fenster, Robert J. Carlezon, William A. Daskalakis, Nikolaos P. Ressler, Kerry J. Nat Commun Article 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. Nature Publishing Group UK 2020-10-14 /pmc/articles/PMC7560654/ /pubmed/33057013 http://dx.doi.org/10.1038/s41467-020-18985-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article McCullough, Kenneth M. Chatzinakos, Chris Hartmann, Jakob Missig, Galen Neve, Rachael L. Fenster, Robert J. Carlezon, William A. Daskalakis, Nikolaos P. Ressler, Kerry J. Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning |
title | Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning |
title_full | Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning |
title_fullStr | Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning |
title_full_unstemmed | Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning |
title_short | Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning |
title_sort | genome-wide translational profiling of amygdala crh-expressing neurons reveals role for creb in fear extinction learning |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560654/ https://www.ncbi.nlm.nih.gov/pubmed/33057013 http://dx.doi.org/10.1038/s41467-020-18985-6 |
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