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

Neuron. 1996 Mar;16(3):611-7. doi: 10.1016/s0896-6273(00)80080-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Isoproterenol / pharmacology*
  • Long-Term Potentiation / drug effects*
  • Models, Neurological
  • Nerve Fibers / drug effects*
  • Protein Kinases / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / drug effects*
  • Time Factors
  • Timolol / pharmacology


  • Receptors, Adrenergic, beta
  • Timolol
  • Protein Kinases
  • Isoproterenol