Epac signaling is required for hippocampus-dependent memory retrieval.
Previously we uncovered a critical role for norepinephrine and beta(1)-adrenergic signaling in hippocampus-dependent memory retrieval. Because the beta(1) receptor couples to G(s), we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cAMP and downstream signaling, we demonstrate that cAMP and two of its targets, protein kinase A (PKA) and exchange protein activated by cAMP (Epac), are both required for retrieval. These findings demonstrate that cAMP signaling through Epac (as well as PKA) plays an essential role in cognition.
Ouyang
Ming
M
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104-6084, USA.
Zhang
Lei
L
Zhu
J Julius
JJ
Schwede
Frank
F
Thomas
Steven A
SA
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005239:Fear; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006624:Hippocampus; D008568:Memory / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction
C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D000242:Cyclic AMP; D004299:Dopamine beta-Hydroxylase; D017868:Cyclic AMP-Dependent Protein Kinases