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Brain Angiotensin type 2 Receptor (AT 2 R) Distribution and Role in Fear Memory
Author(s) -
Yu Zhe,
Krause Eric G,
Marvar Paul J
Publication year - 2017
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.31.1_supplement.854.5
Subject(s) - amygdala , neuroscience , stria terminalis , glutamatergic , prefrontal cortex , psychology , biology , medicine , receptor , glutamate receptor , cognition
Previous clinical studies identify the renin‐angiotensin system (RAS) as a potential therapeutic target in PTSD, however the mechanism(s) are unknown. Brain angiotensin receptors are expressed in limbic and non‐limbic structures and we propose these receptors contribute to modulating inhibitory and excitatory fear circuits important for the consolidation and extinction of fear memory in PTSD. Using a transgenic reporter model (Agtr2‐eGFP BAC mouse), these studies aimed to further characterize and identify the role of the brain angiotensin type 2‐receptor (Agtr2) in fear related brain regions and behavior. We confirmed that Agtr2 is highly expressed in regions such as prefrontal cortex (PFC), bed nucleus of the stria terminalis (BNST), central amygdala (CeA), medial amygdala (MeA) and periaqueductal gray (PAG) ( Figure 1). The average cell density in these brain regions is 277.7±24.2 neurons/mm 2 , which is significantly higher than non‐limbic areas such as dorsal striatum (3.8189±0.4929 neurons/mm 2 ). Moreover, Agtr2‐eGFP positive cells are neuronal, non‐glutamatergic as they are highly co‐localized with the neuronal specific marker NeuN, but not with the astrocytic, microglia and glutamatergic markers GFAP, Iba‐1 and Tbr‐1 respectively. To further investigate the possible function of brain Agtr2, we used Pavlovian fear conditioning, an animal model commonly used to study PTSD (pairing of auditory cues with footshocks). Using C57BL/6J mice (n= 6 / group) we injected the highly selective AT 2 R agonist Compound 21 (C21) bilaterally into the CeA, a critical brain region for the consolidation and extinction of fear memory. Mice receiving C21 into the CeA prior to fear extinction, displayed a trend for enhanced extinction (C21 group − 43% freezing vs. saline − 55% freezing; p=0.19) compared to control. Together, these data provide further evidence characterizing the role of Agtr2 in brain regions important for the consolidation and expression of conditioned fear, which may lead to novel drug targets for the treatment of PTSD and fear related disorders. Support or Funding Information NIH R00 HL107675‐03 AHA 15CSA24340001 1Agtr2 GFP expression in mouse brain. Opt: optic tract; CeA: central amygdala; BLA: basolateral amygdala; MeA: medial amygdala; LV: lateral ventricle; BNST: bed nucleus of the stria terminalis; PVN: paraventricular nucleus; 3V: 3rd ventricle; PAG: periaqueductal gray CPu: caudate putamen