Exchange protein activated directly by cAMP (Epac) is a recently discovered target of the second messenger molecule cAMP. While the functional consequences of activating the cAMP target protein kinase A (PKA) have been extensively characterized in neurons, little is known about the role of Epac activation. Epac is highly expressed in hippocampus and may influence neuroplasticity and learning and memory processes. Infusion of the selective Epac agonist 8-pCPT-cAMP into rat dorsal hippocampus impaired contextual fear conditioning (see SFN abstract Olausson et al.). Biochemical analysis of these hippocampi revealed a subunit-specific cleavage of the extreme C-terminus of the GluR1 AMPA receptor subunit. Subsequent experiments implicated calpain in this effect (see SFN abstract Matsuzaki et al.). These studies suggest that activation of Epac may affect AMPA receptor function and/or dynamics, though further studies are needed to determine the effect of this cleavage on GluR1 receptors. To test the hypothesis th...