Modulation of both the early and the late phase of mossy fiber LTP by the activation of beta-adrenergic receptors

cAMP and the cAMP-dependent protein kinase (PKA) are required in the messy fiber pathway for both the early and the late phase of long-term potentiation (LTP). Since the CA3 region, which is the target of the messy fibers, receives extensive noradrenergic innervation, we examined the role of beta-adrenergic receptors in messy fiber LTP. We found that we could induce an early phase of LTP by pairing isoproterenol, a beta-adrenergic receptor agonist, with a weak train, subthreshold for LTP. This LTP was specific to the messy fiber pathway, was blocked by inhibitors of PKA, and occluded paired-pulse facilitation, suggesting that isoproterenol was acting presynaptically. When isoproterenol was paired with a train that induced only the early phase of LTP, it gave rise to a protein synthesis-dependent late phase. Consistent with these findings, beta-adrenergic antagonists blocked both the late and the early phase of LTP induced by messy fiber stimulation. Thus, beta-adrenegic receptor modulation is important for both phases of messy fiber LTP.