Figure 4.

Prediction of the allosteric kinetics of NMDARs. A, Schematic (top) and detailed mechanism (bottom) of the allosteric kinetics of NMDARs. τ₁ and τ₂ were the time constants of Ca²⁺ · CaM binding to glutamate (Glu)-unbound and Glu-bound NMDARs, respectively, where Ca²⁺ · CaM concentration is 1 μm. Ca²⁺ · CaM bound and Ca²⁺ · CaM unbound NMDARs, which bind to Glu, show the low and high open probability, respectively (Ehlers et al., 1996; Rycroft and Gibb, 2002, 2004b). C₀, C₁, C₂, C₃, C₀ · CaM, C₁ · CaM, C₂ · CaM, and C₃ · CaM are the concentrations of closed-state NMDARs, and O and O · CaM are those of open-state NMDARs (bottom). CaM represents 2 Ca²⁺ · CaM or 3 Ca²⁺ · CaM, and the numerals on arrows are rate constants in μm⁻¹s⁻¹ or s⁻¹, which were set on the basis of the experimental observation (bottom). The complete description of the allosteric kinetics of NMDARs is provided on-line (available at http://www.kurodalab.org/info/STDP/Urakubo2008SI.pdf). B, Time courses of spike timing-dependent [Ca²⁺]_PSD by a single pairing of prespiking and postspiking in the allosteric model with the indicated spike timing in C. C, Spike timing-dependent [Ca²⁺]_PSD in the allosteric model with the indicated τ₁ and τ₂. D, Time courses of spike timing-dependent synaptic conductance in the allosteric model. One hundred pairings of the prespiking and postspiking with 1 Hz were given. E, Spike timing-dependent synaptic conductance in the allosteric model at 2 min (Obs 1) and 60 min (Obs 2) after the onset of stimulation (left). The apparent time constants for LTP and LTD at 2 min were 36.1 and 53.0 ms, respectively. The synaptic conductance with 100 prespikes and postspikes alone at 2 min (black) and 60 min (gray) after the onset of stimulation is also plotted (right, bars). F, Integrated PKA activity (normalized by 3.06) and final CaMKII activity. G, Integrated PP1 activity (normalized by 0.34) and integrated CaN activity (normalized by 1.53).