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Central amygdala angiotensin type 1 receptor (AT 1 R) expressing neurons influence fear extinction
Author(s) -
Yu Zhe,
Kisner Alexandre,
Bhatt Amy,
Polter Abigail,
Marvar Paul
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04072
Subject(s) - amygdala , extinction (optical mineralogy) , neuroscience , receptor , psychology , chemistry , biology , medicine , paleontology
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 (AT 1 R) in fear‐related behavior. Methods Dual immunohistochemistry and whole‐cell patch‐clamp recording were used to characterize AT 1 R‐eGFP + cells in the amygdala of the AT 1 R‐eGFP reporter mouse. Retrograde labeling was employed to detect the connectivity between the AT 1 R‐eGFP cells and other brain regions. Pavlovian fear conditioning and cre‐expressing lentivirus (LV) injection were used to demonstrate the effects of AT 1 R deletion on fear memory in AT 1 R‐floxed mice. Results AT 1 R‐eGFP + neurons in the amygdala were predominantly expressed in the lateral division of the central amygdala (CeL), with little AT 1 R‐eGFP expression in the basolateral amygdala, basomedial amygdala, medial amygdala or medial division of the central amygdala. Characterization of AT 1 R‐eGFP + neurons in the CeL demonstrated that the AT 1 R mainly expressed in GABAergic neurons (99%). Activation of the receptor with angiotensin II can facilitate GABAergic inhibition in the CeL. AT 1 R was deleted via inject cre‐expressing lentivirus into the central amygdala (CeA) of AT 1 R‐Floxed mice. CeA AT 1 R 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<0.05, n=12 and retention tests (53.5% ± 5.3 LV‐GFP v.s. 34.4% ± 5.3 LV‐Cre group, p<0.05, n=13). Furthermore, retrograde labeling revealed that some of the AT 1 R‐eGFP + neurons project to the ventral tegmental area (VTA), an important brain structure to initiate the fear extinction. Conclusion These findings provide evidence for a novel CeL cell type and suggest CeL AT 1 R‐expressing neurons play a role in fear extinction. Future studies are needed to further characterize underlying neurocircuits that likely interact with amygdala expressing AT 1 R neurons.