Long-term effects of brief acute stress on cellular signaling and hippocampal LTP

In a previous study, we reported that a brief exposure to swim stress transforms an electrically induced, protein synthesis-independent early long-term potentiation (early LTP) into a protein synthesis-dependent late LTP ["reinforcement of LTP" in the hippocampal dentate gyrus (DG)] (Korz and Frey, 2003). This transformation depends on activation of mineralocorticoid receptors (MRs) by corticosterone, and on intact basolateral amygdala (BLA) function. Here, we demonstrate that a brief swim experience results in lasting changes in levels of hippocampal cellular signaling molecules that are known to be involved in the induction of late LTP. Within the DG, MRs were rapidly upregulated, whereas glucocorticoid receptor (GR) levels were elevated with a 3 h delay. Levels of phosphorylated mitogen-activated protein kinase 2 (pMAPK2) and p38 MAPK, as well as phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMKII) were enhanced shortly after swim stress and remained elevated until 24 h, whereas levels of phosphorylated cAMP response element-binding protein (pCREB) remained unchanged. MR and GR were upregulated with a longer delay within the CA1 region, whereas levels of pMAPK2 and p38MAPK were rapidly increased, but the former returned to basal levels after 3 h. Levels of pCREB and pCaMKII were maintained in an enhanced state after swim stress. DG-LTP reinforcement requires a serotonergic but not dopaminergic heterosynaptic receptor activation that probably mediates the BLA-dependent modulation of LTP under stress. Thus, molecular alterations induced by specific stress resemble late LTP-related molecular changes. These changes, in interaction with stress-specific heterosynaptic processes, may support the transformation of early LTP into late LTP. The results contribute to the understanding of the rapid consolidation of cellular and possibly systemic memories triggered by stress.