The intracellular Ca²⁺ sensitivity of transmitter release in glutamatergic neocortical boutons

Synaptotagmin-1 (Syt1) and Syt2 are the main calcium (Ca²⁺) sensors triggering synchronous release in the brain. In this work, we studied the mechanisms mediating Syt1-triggered release from neocortical synapses. We measured the Ca²⁺ dependency of release in layer 5 pyramidal neuron synapses by laser photolysis of caged Ca²⁺. Release had high Ca²⁺ 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 Ca²⁺ elevations and high plastic controllability.