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 mossy 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 mossy fibers, receives extensive noradrenergic innervation, we examined the role of beta-adrenergic receptors in mossy 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 mossy 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 mossy fiber stimulation. Thus, beta-adrenergic receptor modulation is important for both phases of mossy fiber LTP.
Huang
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Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Kandel
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ER
D000818:Animals; D007545:Isoproterenol / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008959:Models, Neurological; D009412:Nerve Fibers / Q000187:drug effects*; D011494:Protein Kinases / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D013999:Timolol; D011494:Protein Kinases; D007545:Isoproterenol