Central amygdala angiotensin type 1 receptor (AT1R) expressing neurons influence fear extinction

• Published in: The FASEB journal 2021-05, Vol.35 (S1), p.n/a, Article fasebj.2021.35.S1.04072
• Main Authors: Yu, Zhe, Kisner, Alexandre, Bhatt, Amy, Polter, Abigail, Marvar, Paul
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2021.35.S1.04072

Background The renin‐angiotensin system (RAS) has been implicated in stress‐related disorders (ie., PTSD), however the mechanisms responsible for this connection and the therapeutic potential for targeting the RAS in PTSD remains unknown. Using angiotensin receptor transgenic mice combined with neuroanatomical, behavioral and electrophysiological approaches we examined the role of central amygdala expressing angiotensin II type 1 receptors (AT1R) in fear‐related behavior. Methods Dual immunohistochemistry and whole‐cell patch‐clamp recording were used to characterize AT1R‐eGFP+ cells in the amygdala of the AT1R‐eGFP reporter mouse. Retrograde labeling was employed to detect the connectivity between the AT1R‐eGFP cells and other brain regions. Pavlovian fear conditioning and cre‐expressing lentivirus (LV) injection were used to demonstrate the effects of AT1R deletion on fear memory in AT1R‐floxed mice. Results AT1R‐eGFP+ neurons in the amygdala were predominantly expressed in the lateral division of the central amygdala (CeL), with little AT1R‐eGFP expression in the basolateral amygdala, basomedial amygdala, medial amygdala or medial division of the central amygdala. Characterization of AT1R‐eGFP+ neurons in the CeL demonstrated that the AT1R mainly expressed in GABAergic neurons (99%). Activation of the receptor with angiotensin II can facilitate GABAergic inhibition in the CeL. AT1R was deleted via inject cre‐expressing lentivirus into the central amygdala (CeA) of AT1R‐Floxed mice. CeA AT1R knockdown did not affect fear acquisition, but enhanced the extinction of fear as shown by reduced percent freezing during extinction training (57.04% ± 3.9 LV‐GFP v.s. 42.6% ± 4.1 LV‐Cre group, p