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Stable Mossy Fiber Long-Term Potentiation Requires Calcium Influx at the Granule Cell Soma, Protein Synthesis, and Microtubule-Dependent Axonal Transport

2010; Society for Neuroscience; Volume: 30; Issue: 39 Linguagem: Inglês

10.1523/jneurosci.1847-10.2010

1529-2401

Steven J. Barnes, Thoralf Opitz, Malte Merkens, T. Kelly, Christian von der Brelie, Roland Krueppel, Heinz Beck,

Alzheimer's disease research and treatments

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.