Neocortical High Probability Release Sites Are Formed by Distinct Ca Channel-to-Release Sensor Topographies during Development.

Coupling distances between Ca channels and release sensors regulate vesicular release probability (p). Tight coupling is thought to provide a framework for high p and loose coupling for high plasticity at low p. At synapses investigated during development, coupling distances decrease, thereby increasing p and transmission fidelity. We find that neocortical high-fidelity synapses deviate from these rules. Paired recordings from pyramidal neurons with "slow" and "fast" Ca chelators combined with experimentally constrained simulations suggest that coupling tightens significantly during development. However, fluctuation analysis revealed that neither p (∼0.63) nor the number of release sites (∼8) changes concomitantly. Moreover, the amplitude and time course of presynaptic Ca transients are not different between age groups. These results are explained by high-p release sites with Ca microdomains in young synapses and nanodomains in mature synapses. Thus, at neocortical synapses, a developmental reorganization of the active zone leaves p unaffected, emphasizing developmental and functional synaptic diversity.

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