Long-term potentiation modulates fractal behaviour of quantal release at hippocampal synapses

In this work, we have recorded spontaneous quantal releases from CA3-CA1 postnatal hippocampal primary cultures, 10-15 days after plating, using standard whole-cell configuration (TTx 1µM, APV 25µM, picrotoxin 100µM in the bath). In the past it has been reported that mini series, sequences of release events supposedly independent, display fractal or 1/f behaviour. This suggests that the generation mechanism, albeit spontaneous, can actually trigger a form of "long-range dependence". Our goal was to confirm these findings and evaluate the effect of LTP induction on these nonlinear features. LTP was induced by brief applications of a depolarizing solution (isosmotic 90mM KCl; three 200ms pulses, 5s inter-pulses). This induction protocol produced a ~200% long-lasting increase of mEPSCs frequency. Release series and inter-event intervals were analysed before and after the induction of LTP. Among the analytical methods here used, power spectral density (PSD), Allan factor (AF) and de-trended fluctuations analysis (DFA). In these experiments, the long-term enhancement of quantal release was accompanied by a modulation of 1/f behaviour, with a significant increase in the fractal exponent. Similarly we found that also alpha-latrotoxin (1nM), a very powerful promoter of calcium-independent exocytosis, modulates 1/f behaviour of quantal releases occurring at hippocampal synapses. Taken together, our results suggest that some pre-synaptic mechanisms strictly related to the exocytic machinery and/or to the dynamics of the vesicular pools, primarily involved in LTP expression, are also actively involved in the generation of 1/f behaviour.