Competing calcium sensors orchestrate various patterns of synaptic transmission

Neurotransmission critically depends on both timing and efficacy, enabling neurons to encode information with highly accuracy in millisecond timescales. While synapses often express multiple calcium sensors, such as synaptotagmin-1 (syt1) and synaptotagmin-7 (syt7), the quantitative mechanisms by which these sensors regulate synchronous release (SR) and asynchronous release (AR) remain unresolved. We develop a biophysically detailed stochastic model of a presynaptic bouton that incorporates the distinct calcium-binding kinetics of syt1 and syt7 to dissect their roles in shaping synaptic release. We demonstrate how a rich repertoire of SR and AR patterns is influenced by calcium channel distribution, sensor quantity, the external calcium concentration and buffer properties. Importantly, the interplay between syt1 and syt7— through their distinct calcium affinities and exocytotic kinetics — constitutes a core mechanism for neural transmission. These findings establish calcium partitioning as a core mechanism driving the diverse release patterns of syt1 and syt7, accommodating even more complex multi-sensor environments.