Abstract
Long-term potentiation (LTP) of synaptic strength can be induced by synchronous pre- and post-synaptic activation, and a rise in postsynaptic calcium is essential for induction of LTP. Calcium can enter through both voltage-dependent Ca2+ channels and NMDA-type glutamate receptors, but the relative contributions of these pathways is not known. We have examined this issue in layer V cortical pyramidal neurons, using focal flash photolysis of caged glutamate to mimic synaptic input and two-photon, laser-scanning microscopy to measure calcium levels in dendritic spines. Most of the calcium entry in response to glutamate alone was via voltage-dependent Ca2+ channels, and NMDA receptors accounted for less than 20% of total Ca2+ entry. When glutamate was paired with postsynaptic action potentials, however, the NMDA-receptor-dependent component was selectively amplified. The same is likely to occur during paired physiological pre- and postsynaptic activation, providing a mechanism for the input specificity and Hebbian behavior of LTP.
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Acknowledgements
We thank Ryan Bortolon for excellent technical assistance, David Wokosin and John White of the University of Wisconsin Microscopy Laboratory for their generous help and advice, and Frank Prendergast and the Mayo Foundation for their support. This work was funded by the Howard Hughes Medical Institute (DEC) and a grant from the NIH (DEC).
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Schiller, J., Schiller, Y. & Clapham, D. NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation. Nat Neurosci 1, 114–118 (1998). https://doi.org/10.1038/363
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DOI: https://doi.org/10.1038/363
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