Abstract
Neuronal synaptic connections can be potentiated or depressed by paired pre- and postsynaptic spikes, depending on the spike timing. We show that in cultured rat hippocampal neurons a calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated potentiation process and a calcineurin-mediated depression process can be activated concomitantly by spike triplets or quadruplets. The integration of the two processes critically depends on their activation timing. Depression can cancel previously activated potentiation, whereas potentiation tends to override previously activated depression. The time window for potentiation to dominate is about 70 ms, beyond which the two processes cancel. These results indicate that the signaling machinery underlying spike timing–dependent plasticity (STDP) may be separated into functional modules that are sensitive to the spatiotemporal dynamics (rather than the amount) of calcium influx. The timing dependence of modular interaction provides a quantitative framework for understanding the temporal integration of STDP.
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Acknowledgements
We thank P. Lau for providing data for some STDP experiments; E. Aizenman, K. Kandler, P. Lau and J. Rubin for comments on the manuscript and members of the Bi lab for discussions. This work was supported by grants from Burroughs Wellcome Fund (Career Award in the Biomedical Sciences) and the National Institute of Mental Health (R01 MH066962) to G.Q.B.
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Wang, HX., Gerkin, R., Nauen, D. et al. Coactivation and timing-dependent integration of synaptic potentiation and depression. Nat Neurosci 8, 187–193 (2005). https://doi.org/10.1038/nn1387
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DOI: https://doi.org/10.1038/nn1387
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