Figure 4.

Time course of AMPA receptors during LTP. A, B, With receptors at basal steady state for t < 0, LTP is induced at time t = 0 by making the following changes to the basal GluR1/2 parameter values listed in Table 1 and numerically solving Equations 1–4: binding rate α_I = 0.001 μm² s⁻¹, exocytic rate per receptor κ_I = 0.0556 s⁻¹, and hopping rate h_I = 0.01 μm s⁻¹. Binding site trafficking is also activated according to Equation 11 with c = 0.65. A shows the variation in the total number of receptors (solid black curve) and the number of binding sites (solid green curve) within the PSD, whereas B shows the corresponding variation in the total number of receptors in the ESM (solid black curve) and the number of intracellular receptors (solid gray curve). The contributions from the various receptor types are also shown in A. The number of receptors in the ESM rises transiently because of the exocytosis of intracellular GluR1/2 receptors. Some of these newly exocytosed receptors enter the PSD and are immobilized by the newly available binding sites. These results are consistent with experimentally recorded EPSPs after LTP induction (Hanse and Gustafsson, 1992; O'Connor et al., 2005). C, D, Time course of synaptic receptors (C) and extrasynaptic receptors (D) without synaptic targeting. Labeling of various curves is as in A and B. With receptors at basal steady state at time t < 0, the rate of GluR1/2 exocytosis is increased by setting κ_I = 0.0556 s⁻¹ at time t = 0. However, the hopping rate and binding affinity of GluR1/2 receptors and the number of binding sites remain at basal levels. The concentration in the ESM rises transiently as GluR1/2 receptors from the intracellular pool are exocytosed there, as in the case of LTP, but now there is only a small transient rise in the number of synaptic receptors. These results illustrate that both exocytosis and synaptic targeting are required for LTP. This is consistent with the suggestion that stargazin plays a role in transporting GluR1/2 receptors to the membrane surface, whereas its interaction with PSD-95 is required for synaptic targeting (Schnell et al., 2002). E, Exchange of GluR1/2 and GluR2/3 AMPA receptors. After 1 h of maintaining LTP parameters, all parameters are returned to their basal values except the binding site concentration L, at which time GluR2/3 receptors begin to replace GluR1/2 receptors at the binding sites. These results are consistent with those of McCormack et al. (2006).