Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices

Abstract

LONG-TERM potentiation (LTP) of synaptic transmission in the hippocampus is a widely studied model system for understanding the cellular mechanisms of memory1–6. In region CA1, LTP is triggered postsynaptically7–10 by Ca2+-dependent11,12 activation of protein kinases13,14, but the locus of persistent modification remains controversial15–25. Statistical analysis of synaptic variability has been proposed as a means of settling this debate3,26, although a major obstacle has been the poor signal-to-noise ratio of conventional intracellular recordings. We have applied the whole-cell voltage clamp technique27 to study synaptic transmission in conventional hippocampal slices (compare refs 28–30). Here we report that robust LTP can be recorded with much improved signal resolution and biochemical access to the postsynaptic cell. Prolonged dialysis of the postsynaptic cell blocks the triggering of LTP, with no effect on expression of LTP. The improved signal resolution unmasks a large trial-to-trial variability, reflecting the probabilistic nature of transmitter release31–35. Changes in the synaptic variability, and a decrease in the proportion of synaptic failures during LTP, suggest that transmitter release is significantly enhanced.

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