title: Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus.
abstract: Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2(-/-) mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2(-/-) mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus.
authors.affiliation: Department of Physiology and.
authors.forename: Herman B
authors.initials: HB
authors.lastname: Fernandes
authors.affiliation: Department of Cell and Molecular Biology Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611 and.
authors.forename: Sean
authors.initials: S
authors.lastname: Riordan
authors.affiliation: Department of Physiology and.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Physiology and.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Remmers
authors.affiliation: Department of Physiology and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kraniotis
authors.affiliation: Department of Physiology and.
authors.forename: John J
authors.initials: JJ
authors.lastname: Marshall
authors.affiliation: Department of Cell and Molecular Biology Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611 and.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Kukreja
authors.affiliation: Department of Cell and Molecular Biology Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611 and.
authors.forename: Robert
authors.initials: R
authors.lastname: Vassar
authors.affiliation: Department of Physiology and Department of Neurobiology, Northwestern University Weinberg College of Arts and Sciences, Evanston, Illinois 60208 a-contractor@northwestern.edu.
authors.forename: Anis
authors.identifier: http://orcid.org/0000-0002-5131-2536
authors.initials: A
authors.lastname: Contractor
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C486707:Rapgef4 protein, mouse; D005576:Colforsin; D000242:Cyclic AMP
keywords: Epac2; cAMP; mossy fiber; readily releasable pool