• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway.

Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynaptic function for endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesicles in glutamatergic terminals, an increased frequency of miniature EPSCs, and increased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory.

Pubmed ID: 16237176


  • Kushner SA
  • Elgersma Y
  • Murphy GG
  • Jaarsma D
  • van Woerden GM
  • Hojjati MR
  • Cui Y
  • LeBoutillier JC
  • Marrone DF
  • Choi ES
  • De Zeeuw CI
  • Petit TL
  • Pozzo-Miller L
  • Silva AJ


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

October 19, 2005

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM08042
  • Agency: NIMH NIH HHS, Id: MH063541
  • Agency: NINDS NIH HHS, Id: R01 NS038480
  • Agency: NINDS NIH HHS, Id: R01 NS040593
  • Agency: NINDS NIH HHS, Id: R01 NS040593-09

Mesh Terms

  • Animals
  • Extracellular Signal-Regulated MAP Kinases
  • Humans
  • Learning
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neuronal Plasticity
  • Presynaptic Terminals
  • Proto-Oncogene Proteins p21(ras)
  • Synapsins