RRC ID 57693
Author Inoue R, Abdou K, Hayashi-Tanaka A, Muramatsu SI, Mino K, Inokuchi K, Mori H.
Title Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress.
Journal Elife
Abstract Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.
Volume 7
Published 2018-6-26
DOI 10.7554/eLife.34135
PII 34135
PMID 29941090
PMC PMC6019067
MeSH Acoustic Stimulation Amygdala / anatomy & histology Amygdala / physiology* Animals Conditioning, Psychological Corticosterone / blood Cues Fear / physiology Fear / psychology* Immobilization Integrases / genetics Integrases / metabolism Long-Term Potentiation / physiology Male Memory / physiology* Mice Mice, Inbred C57BL Mice, Transgenic Optogenetics / methods Receptors, Glucocorticoid / deficiency Receptors, Glucocorticoid / genetics* Stress, Psychological / metabolism* Stress, Psychological / physiopathology Stress, Psychological / psychology
IF 7.08
Times Cited 2
Mice RBRC01834