Abstract
In the developing brain, many glutamate synapses have been found to transmit only NMDA receptor–mediated signaling, that is, they are AMPA-silent. This result has been taken to suggest that glutamate synapses are initially AMPA-silent when they are formed, and that AMPA signaling is acquired through activity-dependent synaptic plasticity. The present study on CA3–CA1 synapses in the hippocampus of the neonatal rat suggests that AMPA-silent synapses are created through a form of activity-dependent silencing of AMPA signaling. We found that AMPA signaling, but not NMDA signaling, could be very rapidly silenced by presynaptic electrical stimulation at frequencies commonly used to probe synaptic function (0.05–1 Hz). Although this AMPA silencing required a rise in postsynaptic Ca2+, it did not require activation of NMDA receptors, metabotropic glutamate receptors or voltage-gated calcium channels. The AMPA silencing, possibly explained by a removal of postsynaptic AMPA receptors, could subsequently be reversed by paired presynaptic and postsynaptic activity.
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Acknowledgements
This work was supported by the Swedish Medical Research Council (projects 01580, 12600 and 14842), Göteborgs Läkaresällskap, Åke Wibergs Stiftelse, Svenska Läkaresällskapet and Hjärnfonden. We thank J. Strandberg for participating in initial experiments and L. Groc for helpful discussions.
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Xiao, MY., Wasling, P., Hanse, E. et al. Creation of AMPA-silent synapses in the neonatal hippocampus. Nat Neurosci 7, 236–243 (2004). https://doi.org/10.1038/nn1196
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DOI: https://doi.org/10.1038/nn1196
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