Fluctuations in intracellular calcium responses to action potentials in single en passage presynaptic boutons of layer V neurons in neocortical slices.

The release of neurotransmitter from a nerve terminal on invasion by an action potential shows large trial-to-trial fluctuations. The factors contributing to this variability have not been elucidated clearly. Here, simultaneous patch-clamp and optical measurements from layer V neocortical pyramidal neurons have been used to assess the extent to which the fluctuations in transmitter release may be caused by variability in calcium rise in presynaptic structures. Boutons on axon collaterals were visualized and increases in intracellular calcium, assessed by Fura-2, were observed in response to single action potentials. In some boutons, calcium responses showed trial-to-trial variability and occasional apparent failures despite the faithful conduction of the action potential. These results suggest that a factor contributing to the fluctuation in transmitter release may be the variability with which depolarization of a presynaptic bouton produces an increase in intrabouton calcium.