Requirement of an allosteric kinetics of NMDA receptors for spike timing-dependent plasticity

Hidetoshi Urakubo, Minoru Honda, Robert C. Froemke, Shinya Kuroda

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54 Citations (Scopus)


Spike timing-dependent synaptic plasticity (STDP) plays an important role in neural development and information processing in the brain; however, the mechanism by which spike timing information is encoded into STDP remains unclear. Here, we show that a novel allosteric kinetics of NMDA receptors (NMDARs) is required for STDP. We developed a detailed biophysical model of STDP and found that the model required spike timing-dependent distinct suppression of NMDARs by Ca2+-calmodulin. This led us to predict an allosteric kinetics of NMDARs: a slow and rapid suppression of NMDARs by Ca 2+-calmodulin with prespiking → postspiking and postspiking → prespiking, respectively. We found that the allosteric kinetics, but not the conventional kinetics, is consistent with specific features of amplitudes and peak time of NMDAR-mediated EPSPs in experiments. We found that the allosteric kinetics of NMDARs was also valid for synaptic plasticity induced by more complex spike trains in layer II/III of visual cortex. We extracted an essential synaptic learning rule by reduction of the allosteric STDP model and found that spike timing-dependent bidirectional role of postspiking in synaptic modification, which depends on the allosteric kinetics, is the essential principle in STDP. Thus, we propose a simple hypothesis of the allosteric kinetics of NMDARs that can coherently explain critical features of spike timing-dependent NMDAR-mediated EPSPs and synaptic plasticity.

Original languageEnglish
Pages (from-to)3310-3323
Number of pages14
JournalJournal of Neuroscience
Issue number13
Publication statusPublished - 26-03-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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