Influence of acute stress on auditory fear conditioning is mediated by glucocorticoid receptors in the lateral amygdala

Ran Inoue, Ayumi Tanaka-Hayashi, Hisashi Mori

Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

Stress-induced secretion of glucocorticoid alters memory performance through binding to glucocorticoid receptors (GR) in the specific brains regions including hippocampus and amygdala. The effect of stress on memory performance depends on intensity, duration, and chronicity of stress. Mild stress has a positive effect on memory formation, whereas severe or chronic stress can lead to memory impairment. The mechanisms underlying the effects of stress on memory performance remain largely unclear. Given that lateral nucleus of amygdala (LA) plays critical role in formation of fear memory and physical response to stressful stimuli, we investigated the involvement of GR in LA in the influence of stress on fear memory formation by generating LA-selective GR knockout (LAGRKO) mice. We found that disruption of LAGR impairs standard auditory fear conditioning, which is accompanied by reduced CREB activation in LA 90 min after training. To investigate the influence of LAGRKO on fear memory formation under stressful condition, we exposed mice to restraint stress (RS) 1 h before fear conditioning. Exposure to RS significantly reduced auditory fear memory in both control and LAGRKO mice, however, LAGRKO mice exhibited less decreasing rate of fear memory than did the control mice. Taken together, our findings suggest that LAGR plays a critical role in fear memory formation and in adaptive memory performance response to stress.