Roles of the fast-releasing and the slowly releasing vesicles in synaptic transmission at the calyx of Held.

In the calyx of Held, fast and slow components of neurotransmitter release can be distinguished during a step depolarization. The two components show different sensitivity to molecular/pharmacological manipulations. Here, their roles during a high-frequency train of action potential (AP)-like stimuli were examined by using both deconvolution of EPSCs and presynaptic capacitance measurements. During a 100 Hz train of AP-like stimuli, synchronous release showed a pronounced depression within the 20 stimuli. Asynchronous release persisted during the train, was variable in its amount, and was more prominent during a 300 Hz train. We have shown previously that slowly releasing vesicles were recruited faster than fast-releasing vesicles after depletion. By further slowing recovery of the fast-releasing vesicles by inhibiting calmodulin-dependent processes (Sakaba and Neher, 2001b), the slowly releasing vesicles were isolated during recovery from vesicle depletion. When a high-frequency train was applied, the isolated slowly releasing vesicles were released predominantly asynchronously. In contrast, synchronous release was mediated mainly by the fast-releasing vesicles. The results suggest that fast-releasing vesicles contribute mainly to synchronous release and that depletion of fast-releasing vesicles shape the synaptic depression of the synchronous phase of EPSCs, whereas slowly releasing vesicles are released mainly asynchronously during high-frequency stimulation. The latter is less subject to depression presumably because of a rapid vesicular recruitment process, which is a characteristic of this component.