Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear

Robert C. Hurt; Jacob C. Garrett; Orion P. Keifer; Andrea Linares; Leena Couling; Robert C. Speth; Kerry Ressler; Paul J. Marvar

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Correspondence: Paul J. Marvar, PhD, Department of Pharmacology & Physiology, The George Washington University, 2300 Eye St., NW, Washington, DC 20037, pmarvar@gwu.edu.

Please see the full article for author contributions and acknowledgments.

The authors declare no competing financial interests.

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Research Funding:

This research project was supported by the Emory University Integrated Cellular Imaging Microscopy Core and the following sources of funding: NIH-NHLBI 113905 (R.C.S., A.L., L.C.), Nova Southeastern University President’s Faculty Development Grant (R.C.S., A.L., P.J.M.), Nova Southeastern University Cardiovascular Neuroscience Program (R.C.S., A.L., L.C.), Shared Resource Center supported by NIH-P30 CA51008 and by NCATS 8 UL1 TR000101 (R.C.S.) and NIH R00 HL107675-03 (P.J.M).

Keywords:

Life Sciences & Biomedicine
Behavioral Sciences
Neurosciences
Neurosciences & Neurology
Amygdala
angiotensin II
angiotensin II receptor type 1
blood pressure
cardiovascular
corticotropin-releasing factor
extinction
fear
paraventricular nucleus
PTSD
DORSAL RAPHE NUCLEUS
PANIC-LIKE RESPONSES
MEMORY CONSOLIDATION
STRIA TERMINALIS

Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear

Robert C. Hurt, Emory University

Jacob C. Garrett, Emory University

Orion P. Keifer, Emory University

Andrea Linares, Nova Southeastern University

Leena Couling, Nova Southeastern University

Robert C. Speth, Nova Southeastern University

Kerry Ressler, Emory University

Paul J. Marvar, George Washington University

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Journal Title:

Genes, Brain and Behavior

Volume:

Volume 14, Number 7

Publisher:

Wiley | 2015-09-01, Pages 526-533

Type of Work:

Article | Post-print: After Peer Review

Permanent URL:

https://pid.emory.edu/ark:/25593/rr9cq

Publisher DOI:

http://doi.org/10.1111/gbb.12235

Abstract:

Although generally associated with cardiovascular regulation, angiotensin II receptor type 1 (AT1aR) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post-traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin-releasing factor (CRF)-expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1aR signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1aR gene from its CRF-releasing cells (CRF-AT1aR(−/−)). These mice exhibit normal baseline heart rate, blood pressure, anxiety, and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF-AT1aR(−/−) mice exhibit less freezing than wild type mice during tests of conditioned fear expression—an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1R activity in CRF-expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1R antagonists may act to modulate fear extinction.

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Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear

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