Mechanisms for Acute Stress-Induced Enhancement of Glutamatergic Transmission and Working Memory

摘要

Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and surface expression of NMDARs and AMPARs in PFC pyramidal neurons via a mechanism depending on the induction of serum- and glucocorticoid-inducible kinase (SGK) and the activation of Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Working memory, a key function relying on glutamatergic transmission in PFC, is enhanced in acutely stressed animals via a SGK-dependent mechanism. These results suggest that acute stress, by activating glucocorticoid receptors (GRs), increases the trafficking and function of NMDARs and AMPARs via SGK/Rab4 signaling, which leads to the potentiated synaptic transmission, thereby facilitating cognitive processes mediated by the PFC.