Abstract
Spike-timing-dependent synaptic plasticity (STDP), which depends on the relative timing of pre- and postsynaptic spiking, plays an important role in neural development and information storage. However, the mechanisms by which spike-timing information is encoded into STDP remains unclear. Here we show that a novel allosteric kinetics of N-methyl-D-aspartate receptors (NMDARs) codes spike-timing information into STDP (Figure). We developed a biophysical model of STDP, and found a requirement of slow and rapid suppression of NMDARs by Ca2+·calmodulin with pre- -> post- and post- -> pre-spiking, respectively, which led us to predict an allosteric kinetics of NMDARs during induction of synaptic plasticity. We experimentally validated the allosteric kinetics by examining peak-amplitudes and time of NMDAR-mediated EPSPs. The allosteric kinetics of NMDARs was also experimentally valid for synaptic plasticity induced by more complex spike trains. Simplification of the model revealed that intracellular Ca2+ concentration, at the time when glutamate binds to NMDAR, is the dominant spike-timing information carrier. These findings demonstrate that the simple allosteric kinetics of NMDARs governs the coding of complex spike-timing information into long-term changes in synaptic strength, which may restructure neural circuits and embed experiences into the brain. In this symposium, we discuss the possible interaction between experiments and simulation in terms of synaptic plasticity. [J Physiol Sci. 2008;58 Suppl:S32]
