The intracellular Ca 2+ sensitivity of transmitter release from neocortical boutons

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Synaptotagmin 1 (Syt1) and Syt2 are the main Ca 2+ sensors triggering synchronous release in the brain. The Ca 2+ -sensitivity of Syt2-triggered release has been studied in detail. However, for Syt1, the dominating isoform in the neocortex, quantitative detail is lacking. We measured the Ca 2+ -dependency of Syt1-triggered release at layer 5 pyramidal neuron synapses by laser photolysis of caged Ca 2+ . Syt1-triggered release had high Ca 2+ affinity and positive cooperativity (EC 50 , 20 μM; Hill coefficient, 3.57). It was steep in a dynamic range between ∼10 and ∼30 μM that was covered by action potential-evoked release. A kinetic model reveals significant differences to models of Syt2-triggered release. Our results suggest that Syt1 optimizes neocortical synapses for high reliability at moderate local Ca 2+ elevations and for high plastic controllability.

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