Differences in the magnitude of long-term potentiation produced by theta burst and high frequency stimulation protocols matched in stimulus number

Theta-burst stimulation (TBS: four pulses at 100 Hz repeated with 200 ms inter-burst-intervals) and another commonly used high-frequency stimulation protocol (HFS: 1 s burst of equally spaced pulses at 100 Hz) were compared for the magnitude of LTP produced in rat hippocampal slices. The total number of pulses applied during tetanus (TET) was either 40, 100, 200, or 300. In a conventional analysis of the last 10 min of the post-TET period, a two-way ANOVA revealed no difference either in LTP of the field excitatory post-synaptic potential (fEPSP) between TBS and HFS or differences across pulse number at 40, 100, or 200 pulses. At 300 pulses, there was a significant main effect by pulse number but not by protocol. A linear regression analysis showed that stimulation protocol accounted for only about 10% of the change in magnitude while pulse number contributed to 30% of the change. However, when an extended analysis of the same data was performed across the entire post-TET period with a repeated-measure ANOVA, a small but persistent increase in TBS over HFS at 200 pulses was significant. A difference between TBS and HFS at 300 pulses that occurred only during the early phase of LTP was also significant. These results suggest that, over a range of stimuli, the number of pulses in an induction protocol, rather than the pattern of stimulation, determines the magnitude of late phase LTP, while TBS produces greater potentiation than HFS in the early phase of LTP with higher TET number.