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About the Authors:
Eric M. Prager
Affiliation: Program in Neuroscience, Uniformed Services University, Bethesda, Maryland, United States of America
Jennifer Brielmaier
Affiliation: Department of Psychiatry, Uniformed Services University, Bethesda, Maryland, United States of America
Hadley C. Bergstrom
Affiliation: Department of Psychiatry, Uniformed Services University, Bethesda, Maryland, United States of America
Jennifer McGuire
Affiliation: Department of Psychiatry, Uniformed Services University, Bethesda, Maryland, United States of America
Luke R. Johnson
* E-mail: [email protected]
Affiliations Program in Neuroscience, Uniformed Services University, Bethesda, Maryland, United States of America, Department of Psychiatry, Uniformed Services University, Bethesda, Maryland, United States of America, Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, Maryland, United States of America
Introduction
The amygdala, particularly the lateral nucleus, (LA) is established as a site for the acquisition and storage of conditioned fear memory and a trigger of the stress response [1]–[5]. The expression of conditioned fear includes amygdala dependent activation of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA-axis increases blood concentration of corticosterone in rodents, which in turn feeds back to the brain including the amygdala where it binds to both mineralocorticoid (MRs) and glucocorticoid receptors (GRs) [6]–[8]. In the hippocampus, MR and GR activation elicits both rapid, non-genomic effects [8]-[10] resulting in changes to synaptic transmission. Cytosolic MR and GR also translocate to the nucleus upon activation, which results in changes in gene transcription [11]–[13]. The cellular mechanisms of MR and GR signaling in the LA are not fully understood. However, recent evidence suggests the LA likely contains signaling mechanisms that include both classic nuclear MR and GR signaling as well as direct signaling from the synapse via membrane receptors mechanisms [7], [8], [14], [15], which regulates the fear response and influence fear related behaviors [16]–[22].
Both MR and GR regulate the acquisition and consolidation of fearful memories and may be implicated in stress related disorders [4], [23]–[26]. Behavioral evidence suggests that activation of the MR and GR may modulate the acquisition and consolidation of fear memories [8], [18], [27]–[33]. Membrane MR (mMR) and GR (mGR) may also be implicated in the formation of fear memories. Corticosterone (CORT) conjugated to a high molecular weight substance (e.g., bovine serum albumin; BSA) [34] prevents CORT from entering the cell and can be used to study the...