Fig. 5

Acute Psychological Stress: The Role of Cortisol and Kinases in Memory Formation. During acute stress (depicted by mustard/dark yellow arrows), rapidly increased levels of cortisol can activate GRs that increase surface expression of NMDA and AMPA receptors (nongenomic memory effect). Upregulated Ca²⁺/Calmodulin dependent kinases IIα pathway activates CREB mechanism (fast indirect epigenetic effect related to neuropsychiatric outcomes such as anxiety and increased risk for post-traumatic stress disorder). At the same time, activated ERK/MAPK inhibits stathmin via phosphorylation; that stabilizes microtubules and, in turn, activates incorporation of the GluA2 subunit (AMPA receptor) to synaptic sites, which is necessary for long-term memory formation yet supports fear conditioning/learning. See Fig. 4 for the path [1]–[4]. cAMP, cyclic AMP; CREB, cAMP response element-binding protein; ERK, extracellular regulated kinase, aka mitogen-activated protein kinase (MAPK); GR, glucocorticoid receptors; GRE, glucocorticoid response elements; PO₃², phosphorylation