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. 2015 Oct 7;7:17. doi: 10.3389/fnsyn.2015.00017

Figure 8.

Figure 8

Snapshots of simulated glutamate release and postsynaptic calcium dynamics at different times during an EPSP+bAP stimulus. We used Cell Blender (see Methods Section) to visualize simulated glutamate release and calcium entry into spine #37 (see Figure 4A) during an EPSP+bAP stimulus. All other components of the neuropil were present in the simulation but are not displayed in the visualization. All scale bars are 0.25 μm. (A–C) Time-lapse sequence of glutamate (cyan dots) released onto a dendritic spine with unbound AMPARs (smaller, dark-green glyphs) and unbound NMDARs (larger, dark-blue glyphs). Snapshots (A–C) were made from data generated by MCell during a single trial and taken at 1, 200 μs, and 17 ms after glutamate release, respectively. Glutamate diffused rapidly throughout the synaptic cleft, binding to AMPARs and NMDARs. Singly bound AMPARs are shown as medium-green glyphs, doubly bound AMPARs as bright-green glyphs, open AMPARs as yellow glyphs, and desensitized AMPARs as black glyphs. Singly bound NMDARs are shown as medium-blue glyphs, doubly bound NMDARs as bright-blue glyphs, and open NMDARs as white glyphs. During this trial the peak of AMPAR activation occurred at ~200 μs and the peak of NMDAR activation occurred at ~17 ms when a single NMDAR flickered open (white glyph indicated by white arrow in C). (D–F) Time-lapse sequence of glutamate decay and calcium influx after stimulation. Snapshots for (D–F) were made from data generated by MCell during a single trial and taken at 100 μs, 17, and 100 ms after glutamate release, respectively. The presynaptic axon (green) on the right makes an en passant synapse with the postsynaptic spine (translucent yellow) on the left. Free glutamate molecules (cyan dots) diffuse from the synaptic cleft within a few microseconds and are taken up within a 100 ms by astroglial transporters (not visualized but present in the simulation). Some glutamate remains bound and activates NMDARs for many tens of microseconds allowing influx of calcium (white dots) as NMDARs flicker open and closed. In this example, calcium entered the spine through a single open NMDAR and was cleared from the spine head via calcium pumps in the spine membrane and by diffusion through the spine neck.