Coactivation and timing-dependent integration of synaptic potentiation and depression

Huai Xing Wang, Richard C. Gerkin, David W. Nauen, Guo Qiang Bi

Research output: Contribution to journalArticlepeer-review

213 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)187-193
Number of pages7
JournalNature neuroscience
Issue number2
StatePublished - Feb 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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