Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP

Repetitive activation of hippocampal mossy fibers evokes a long-term potentiation (LTP) of synaptic responses in pyramidal cells in the CA3 region that is independent of N-methyl-D-aspartate receptor activation. Previous results suggest that the site for both the induction and expression of this form of LTP is presynaptic. Experimental elevation of cyclic adenosine 3',5'-monophosphate (cAMP) both mimics and interferes with tetanus-induced mossy fiber LTP, and blockers of the cAMP cascade block mossy fiber LTP. It is proposed that calcium entry into the presynaptic terminal may activate Ca(2+)-calmodulin-sensitive adenylyl cyclase I which, through protein kinase A, causes a persistent enhancement of evoked glutamate release.