Rapid change of quantal size in PC-12 cells detected by neural networks

The basic building block of synaptic transmission—the number of molecules released per vesicle (quantal size (QS)) often changes with stimulation, but there is no agreement about what factors regulate it. To throw more light on this problem spontaneous quantal release was recorded amperometrically in PC-12 cells. Amperometric current spikes, representing single vesicle release, were detected by thresholding and were separated from spurious events on the basis of their amplitude and time course using a pattern recognition system based on the principal component neural network methods. The frequency of current spikes, their amplitude, quantal size, rise time and decay time were typically non-stationary, even in the absence of stimulation. Their running values changed much more than those of memoryless stationary random data with the same probability density distribution. Irrespective of how much the quantal size, rise and decay times varied, their amplitude dependence remained constant, or changed with a very different time course. In conclusion, the quantal size is highly labile in PC-12 cells. The lability does not appear to result from the changes of fusion pore dynamics or the mechanism of release of vesicular content, but because of the preferential release of large vesicles.