Figure 1.

Temporal integration of NMDAR responses evoked by a sequence of glutamate release events. (A and B) Examples of NMDAR activation kinetics (upper traces in A and B) evoked by a series of brief glutamate release (blue trace; concentration time course during release magnified in A, inset) at two average event frequencies, 1 Hz (A) and 10 Hz (B). (Black, red, and green traces, respectively) Double-bound, open, and desensitized states of NMDARs. NMDAR kinetics were calculated using a multistep, single-compartment model (Materials and Methods). (C) Average occupancy of NMDARs at different release frequencies, with and without 0.2 mM glutamate transporters present (solid and open circles, respectively; NMDAR activation by glutamate assumes sufficient membrane depolarization to fully relieve the Mg²⁺ block). (Dotted line) Activation value under the ambient glutamate level equilibrated under steady-state glutamate supply (leakage) in the presence of transporters. The supply rate provides the amount of glutamate equivalent to that averaged over time during individual releases at various frequencies as shown. To see this figure in color, go online.