The intracellular Ca<sup>2+</sup> sensitivity of transmitter release in glutamatergic neocortical boutons.

Bornschein, Grit; Brachtendorf, Simone; Reinert, Anja; Eshra, Abdelmoneim; Kraft, Robert; Hirrlinger, Johannes; Eilers, Jens; Hallermann, Stefan et al. · Science · 2025

basic_science · Level V

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Abstract

Synaptotagmin-1 (Syt1) and Syt2 are the main calcium (Ca<sup>2+</sup>) sensors triggering synchronous release in the brain. In this work, we studied the mechanisms mediating Syt1-triggered release from neocortical synapses. We measured the Ca<sup>2+</sup> dependency of release in layer 5 pyramidal neuron synapses by laser photolysis of caged Ca<sup>2+</sup>. Release had high Ca<sup>2+</sup> affinity and positive cooperativity. Measurements at cerebellar Purkinje cell synapses and kinetic models indicate substantial differences compared with Syt2-triggered release. Our results suggest that Syt1-controlled release machineries are optimized for high reliability at moderate Ca<sup>2+</sup> elevations and high plastic controllability.

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