TY - JOUR TI - Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress AU - Inoue, Ran AU - Abdou, Kareem AU - Hayashi-Tanaka, Ayumi AU - Muramatsu, Shin-ichi AU - Mino, Kaori AU - Inokuchi, Kaoru AU - Mori, Hisashi A2 - Kauer, Julie A VL - 7 PY - 2018 DA - 2018/06/26 SP - e34135 C1 - eLife 2018;7:e34135 DO - 10.7554/eLife.34135 UR - https://doi.org/10.7554/eLife.34135 AB - 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. KW - glucocorticoid receptor KW - metaplasticity KW - lateral amygdala KW - auditory fear conditioning KW - stress JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -