Epac2 mediates cAMP-dependent potentiation of neurotransmission in the hippocampus

Herman B. Fernandes, Sean Riordan, Toshihiro Nomura, Christine L. Remmers, Stephen Kraniotis, John J. Marshall, Lokesh Kukreja, Robert Vassar, Anis Contractor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6544-6553
Number of pages10
JournalJournal of Neuroscience
Issue number16
StatePublished - Apr 22 2015


  • Epac2
  • Mossy fiber
  • Readily releasable pool
  • cAMP

ASJC Scopus subject areas

  • General Neuroscience


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