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bioRxiv · 10.1101/233577

Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress

Inoue, R.·Abdou, K.·Hayashi-Tanaka, A.·Muramatsu, S.-i.·Mino, K.·Inokuchi, K.·Mori, H.
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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.

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Inoue, R., Abdou, K., Hayashi-Tanaka, A., Muramatsu, S.-i., Mino, K., Inokuchi, K., Mori, H.. 2017-12-14. Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress. https://doi.org/10.1101/233577

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