Effectors of presynaptic cAMP dependent potentiation at mossy fiber synapses

Synaptic plasticity in the hippocampus is critical to the formation, storage and retrieval of episodic memories. The separate regions of the hippocampus have evolved to play distinct roles in spatial navigation, contextual memories, social memories, and our ability to separate patterns or complete patterns to reconstruct partial memories. In particular the dentate and CA3 regions of the hippocampus are involved in pattern separation that is vital to the integrity of episodic memories. At the center of this region are the mossy fiber afferents that make conditional detonator synapses onto CA3 pyramidal neurons, which have a distinct form of presynaptic cAMP dependent plasticity. Despite the importance of cAMP plasticity to memory formation and retrieval in the CA3 the exact molecular mechanisms underlying MF LTP have yet to be uncovered. The premise of this research builds upon our finding that there are at least two downstream cAMP effectors, PKA (protein kinase A) and Epac2 (exchange protein directly activated by cAMP 2), that contribute to cAMP dependent MF LTP. Despite these findings it is still not known how signaling by each of these effectors results in elevated release from MF synapses and, what are the important targets and substrates that are involved in MF LTP.