Differential Stress Induced C-Fos Expression and Identification of Region-specific MiRNA-mRNA Networks in the Dorsal Raphe and Amygdala of High-responder/low-responder Rats

Overview

Journal Behav Brain Res

Specialties Neurology
Psychology
Social Sciences

Date 2016 Nov 21

PMID 27865919

Citations 20

Authors

Joshua L Cohen

Anooshah E Ata

Nateka L Jackson

Elizabeth J Rahn

Ryne C Ramaker

Sara Cooper

Ilan A Kerman

Sarah M Clinton

Affiliations

Soon will be listed here.

Abstract

Chronic stress triggers a variety of physical and mental health problems, and how individuals cope with stress influences risk for emotional disorders. To investigate molecular mechanisms underlying distinct stress coping styles, we utilized rats that were selectively-bred for differences in emotionality and stress reactivity. We show that high novelty responding (HR) rats readily bury a shock probe in the defensive burying test, a measure of proactive stress coping behavior, while low novelty responding (LR) rats exhibit enhanced immobility, a measure of reactive coping. Shock exposure in the defensive burying test elicited greater activation of HR rats' caudal dorsal raphe serotonergic cells compared to LRs, but lead to more pronounced activation throughout LRs' amygdala (lateral, basolateral, central, and basomedial nuclei) compared to HRs. RNA-sequencing revealed 271 mRNA transcripts and 33 microRNA species that were differentially expressed in HR/LR raphe and amygdala. We mapped potential microRNA-mRNA networks by correlating and clustering mRNA and microRNA expression and identified networks that differed in either the HR/LR dorsal raphe or amygdala. A dorsal raphe network linked three microRNAs which were down-regulated in LRs (miR-206-3p, miR-3559-5p, and miR-378a-3p) to repression of genes related to microglia and immune response (Cd74, Cyth4, Nckap1l, and Rac2), the genes themselves were up-regulated in LR dorsal raphe. In the amygdala, another network linked miR-124-5p, miR-146a-5p, miR-3068-3p, miR-380-5p, miR-539-3p, and miR-7a-1-3p with repression of chromatin remodeling-related genes (Cenpk, Cenpq, Itgb3bp, and Mis18a). Overall this work highlights potential drivers of gene-networks and downstream molecular pathways within the raphe and amygdala that contribute to individual differences in stress coping styles and stress vulnerabilities.

Citing Articles

Chronic mild stress induces differential depression-like symptoms and c-Fos and 5HT1A protein levels in high-anxiety female Long Evans rats.

Calhoun C, Lattouf C, Lewis V, Barrientos H, Donaldson S Behav Brain Res. 2022; 438:114202.

PMID: 36343695 PMC: 9990717. DOI: 10.1016/j.bbr.2022.114202.

Using social rank as the lens to focus on the neural circuitry driving stress coping styles.

LeClair K, Russo S Curr Opin Neurobiol. 2021; 68:167-180.

PMID: 33930622 PMC: 8883325. DOI: 10.1016/j.conb.2021.03.007.

Modeling heritability of temperamental differences, stress reactivity, and risk for anxiety and depression: Relevance to research domain criteria (RDoC).

Clinton S, Shupe E, Glover M, Unroe K, McCoy C, Cohen J Eur J Neurosci. 2021; 55(9-10):2076-2107.

PMID: 33629390 PMC: 8382785. DOI: 10.1111/ejn.15158.

Examining the Role of Microbiota in Emotional Behavior: Antibiotic Treatment Exacerbates Anxiety in High Anxiety-Prone Male Rats.

Glover M, Cohen J, Singer J, Sabbagh M, Rainville J, Hyland M Neuroscience. 2021; 459:179-197.

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Inborn differences in emotional behavior coincide with alterations in hypothalamic paraventricular motor projections.

Shupe E, Glover M, Unroe K, Kerman I, Clinton S Eur J Neurosci. 2020; 53(3):814-826.

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