Fig. 5. Proposed synaptic organization and events.

a Schematic of proposed synaptic organization and events. Docked vesicles are found throughout the active zone. AMPA receptors are found toward the edge, while NMDA receptors are biased toward the center. Synchronous fusion begins within hundreds of microseconds near the AMPA receptor cluster. Released glutamate activates AMPA receptors, which, in turn, depolarizes the membrane and alleviates the Mg²⁺ block of NMDA receptors. Between 5 and 11 ms, residual calcium triggers asynchronous fusion, preferentially toward the center of the active zone and across from the NMDA receptor cluster, favoring the NMDA receptors. Although shown here as taking place in the same active zone, the degree to which synchronous and asynchronous release may occur at the same active zone after a single action potential is unknown. This transsynaptic organization allows the maximal depolarization of the postsynaptic membrane and efficient activation of NMDA receptors.