Figure 4.

Spatial and temporal integration of NMDAR activation during glutamate release. (A) Time course of the NMDAR activation (open state with no Mg²⁺ block) resulting from six release events occurring at different frequencies within the area and, separately, with the equivalent amount of ambient (leaking) glutamate, as indicated; glutamate transporters are enabled at 0.2 mM extracellular concentration. The frequency values shown indicate events per the entire simulation arena: the frequency of events per synapse is therefore 54-times lower. Average of n = 8 runs (except for 4 Hz^∗ with n = 64; this test frequency was chosen to test the outcome stability (53)). Sync is the synchronous release from six arbitrarily chosen synaptic sites. Traces at higher frequencies and for ambient glutamate are curtailed at 100 ms due to excessive demand for computing time and because the 2-Hz trace at 100–200 ms should be representative of other cases postrelease. (B) The proportion of activated NMDARs outside releasing (active) synapses at two characteristic frequencies, as indicated. Note the monotonic increase of the activation level reflecting the buildup of spatiotemporal glutamate signal integrating over the tissue volume. (C) Time course of the average concentration of free glutamate during and after six release events at different frequencies (within the area of 54 synapses), as indicated. (Gray lines) Individual runs (n = 8); (black line) average; and (dotted gray line) 50 nM (estimated ambient level of glutamate in situ). The rebound of glutamate concentration from its lowest value reflects unbinding of glutamate molecules from transporters after an initial transporter-glutamate buffering event, as described in Lehre and Rusakov (33). To see this figure in color, go online.