Neocortical High Probability Release Sites are Formed by Distinct Ca <sup>2+</sup> Channel to Release Sensor Topographies During Development

Abstract

Coupling distances between Ca2+ channels and release sensors regulate the vesicular release probability (pr). Tight coupling is thought to provide a framework for high pr and loose coupling for high plasticity at low pr. At synapses investigated during development, coupling distances decreased, thereby, increasing pr and transfer fidelity. We found neocortical high-fidelity synapses to deviate from these rules. Paired recordings from pyramidal neurons with ‘slow’ and ‘fast’ Ca2+ chelators combined with experimentally constrained simulations suggest that coupling tightened significantly during development. However, fluctuation analysis revealed that neither pr (~0.63) nor the number of release sites (~8) changed concomitantly, although amplitude and time-course of presynaptic Ca2+ transients were not different between age groups. These results are explained by high-pr release sites with Ca2+ microdomains in young and nanodomains in mature synapses. Thus, developmental reorganization of the active zone left pr unaffected at a neocortical synapse, emphasizing developmental and functional synaptic diversity.