Competing calcium sensors orchestrate various patterns of synaptic transmission
Li, Y.; Lallouette, J.; Hepburn, I.; Chen, W.; De Schutter, E.
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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.
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