Fig. 1

Epigenetic Mechanisms of Memory Alteration Following Acute Psychological Stress. Simplified and schematic model of indirect epigenetic mechanisms for fast (< 1 h) nongenomic effects induced by membrane-associate receptors during acute stress. Increased levels of NE bind to BR (namely β2) and rapidly increase Ca²⁺ influx and cAMP and Ca²⁺/MK activation, that triggers PKA to modulate synaptic activity (see Fig. 4) and phosphorylate CREB, which activates transcription and gene expression linked to neuronal plasticity, spatial memory, and long-term memory formation. This mechanism supports fear conditioning/learning, whereas severe stress can decrease initially activated Ca²⁺/MK, which relates to poor memory. Estradiol can activate ERs (mostly type β) linked to fear learning/conditioning via ERK/MAPK pathways which affect post-translational gene regulation via histone acetylation. In the amygdala, independently of sex-hormone levels, short photoperiod reduces melatonin and thus increases estradiol-induced phosphorylation of CREB (males) and ERK aka MAPK (females) linked to aggression. In acute stress, high estradiol levels in proestrus are linked to the prefrontal cortex memory deficit and altered glutamate signalling, potentially due to hyperactivated Ca²⁺/MK. Ca²⁺/MK, Ca²⁺/Calmodulin dependent kinases IIα; CH₃CO, acetylation; CREB, cAMP response element-binding protein; ERK, extracellular regulated kinase, aka mitogen-activated protein kinase (MAPK); ER, estrogen receptors; GR, glucocorticoid receptor; H, histone; NE, norepinephrine; PO₃², phosphorylation; PKA, protein kinase A