Stable mossy fiber long-term potentiation requires calcium influx at the granule cell soma, protein synthesis, and microtubule-dependent axonal transport.
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.
Barnes
Steven J
SJ
Department of Epileptology, University of Bonn, D-53105 Bonn, Germany.
Opitz
Thoralf
T
Merkens
Malte
M
Kelly
Tony
T
von der Brelie
Christian
C
Krueppel
Roland
R
Beck
Heinz
H
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009924:Organ Culture Techniques
D009419:Nerve Tissue Proteins; D002118:Calcium