Figure 4.

Lateral diffusion can counter desensitisation of synaptic AMPARs during repetitive releases. (a) Schematic showing that following glutamate release (red cloud) the activated AMPARs (desensitised over time τ_des) are exchanged (over time τ_dif) for resting (naive, non-activated) receptors (before the next release event in time τ_rel); (adapted, with permission, from [107]). (b) In the calyx of Held, AMPAR recovery from desensitisation shortens drastically from P7 to P21, as shown by paired-pulse experiments (left), in which AMPAR desensitisation can be suppressed pharmacologically by cyclothiazide (CTZ, right); (reproduced, with permission, from [110]). (c) Simulated profile of desensitised AMPARs inside the synaptic cleft 1 ms post-release predicts 40–50% receptor desensitisation; colour scale shows receptor fraction (reproduced, with permission, from [13]). (d) Time-course of AMPAR desensitisation (left) and activation (right) as predicted by a Monte Carlo model [18] during repetitive releases of glutamate at 20, 100, and 200 Hz suggests a significant impact upon synaptic responses (with little effect from transporters, Tr); (reproduced, with permission, from [18]).