title: Epac activation initiates associative odor preference memories in the rat pup.
abstract: Here we examine the role of the exchange protein directly activated by cAMP (Epac) in β-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac activation produced both short-term (STM) and long-term (LTM) odor preference memories. Training using β-adrenergic-activation paired with odor recruited rapid and transient ERK phosphorylation consistent with a role for Epac activation in normal learning. An ERK antagonist prevented intermediate-term memory (ITM) and LTM, but not STM. Epac agonist infusions induced ERK phosphorylation in the mitral cell layer, in the inner half of the dendritic external plexiform layer, in the glomeruli and, patchily, among granule cells. Increased CREB phosphorylation in the mitral and granule cell layers was also seen. Simultaneous blockade of both ERK and CREB pathways prevented any long-term β-adrenergic activated odor preference memory, while LTM deficits associated with blocking only one pathway were prevented by stronger β-adrenergic activation. These results suggest that Epac and PKA play parallel and independent, as well as likely synergistic, roles in creating cAMP-dependent associative memory in rat pups. They further implicate a novel ERK-independent pathway in the mediation of STM by Epac.
authors.affiliation: Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6 Canada.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Grimes
authors.affiliation: Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6 Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Powell
authors.affiliation: Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6 Canada.
authors.forename: Sandra Mohammed
authors.initials: SM
authors.lastname: Gutierrez
authors.affiliation: Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6 Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Darby-King
authors.affiliation: Department of Psychology, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6 Canada.
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Harley
authors.affiliation: Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6 Canada john.mclean@med.mun.ca.
authors.forename: John H
authors.initials: JH
authors.lastname: McLean
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009812:Odorants; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
chemical_list: C473217:8-(4-chloro-phenylthio)-2'-O-methyladenosine-3'-5'-cyclic monophosphate; D020662:Guanine Nucleotide Exchange Factors; C526973:Rapgef3 protein, rat; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1