Stable mossy fiber long-term potentiation requires calcium influx at the granule cell soma, protein synthesis, and microtubule-dependent axonal transport

J Neurosci. 2010 Sep 29;30(39):12996-3004. doi: 10.1523/JNEUROSCI.1847-10.2010.


The synapses formed by the mossy fiber (MF) axons of hippocampal dentate gyrus granule neurons onto CA3 pyramidal neurons exhibit an intriguing form of experience-dependent synaptic plasticity that is induced and expressed presynaptically. In contrast to most other CNS synapses, long-term potentiation (LTP) at the MF-CA3 synapse is readily induced even during blockade of postsynaptic glutamate receptors. Furthermore, blocking voltage-gated Ca(2+) channels prevents MF-LTP, supporting an involvement of presynaptic Ca(2+) signaling via voltage-gated Ca(2+) channels in MF-LTP induction. We examined the contribution of activity in both dentate granule cell somata and MF terminals to MF-LTP. We found that the induction of stable MF-LTP requires tetanization-induced action potentials not only at MF boutons, but also at dentate granule cell somata. Similarly, blocking Ca(2+) influx via voltage-gated Ca(2+) channels only at the granule cell soma was sufficient to disrupt MF-LTP. Finally, blocking protein synthesis or blocking fast axonal transport mechanisms via disruption of axonal tubulin filaments resulted in decremental MF-LTP. Collectively, these data suggest that-in addition to Ca(2+) influx at the MF terminals-induction of MF synaptic plasticity requires action potential-dependent Ca(2+) signaling at granule cell somata, protein synthesis, and fast axonal transport along MFs. A parsimonious interpretation of these results is that somatic activity triggers protein synthesis at the soma; newly synthesized proteins are then transported to MF terminals, where they contribute to the stabilization of MF-LTP. Finally, the present data imply that synaptic plasticity at the MF-CA3 synapse can be affected by local modulation of somatic and presynaptic Ca(2+) channel activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport / physiology*
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / metabolism
  • CA3 Region, Hippocampal / physiology*
  • Calcium / metabolism*
  • Calcium / physiology
  • Calcium Signaling / physiology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / physiology*
  • Excitatory Postsynaptic Potentials / physiology
  • Long-Term Potentiation / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubules / physiology*
  • Mossy Fibers, Hippocampal / metabolism
  • Mossy Fibers, Hippocampal / physiology*
  • Nerve Tissue Proteins / biosynthesis*
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neural Pathways / physiology
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Neurons / physiology
  • Organ Culture Techniques


  • Nerve Tissue Proteins
  • Calcium