Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. I. Stimulus intensity

Paired pulse stimulation of the perforant path provides a measure of inhibition of dentate granule cell field potentials that is reflected in the depression of the second (test) population spike (PS) relative to the first (conditioning) PS. The assumption that the strength of paired pulse depression is dependent upon the amplitude of the conditioning PS was investigated by increasing the stimulus intensity of both pulses (5-100% of maximum, Experiment 1), or by increasing the stimulus intensity of the conditioning pulse (5-100%) while maintaining a constant stimulus intensity of the test pulse (50%, Experiment 2). In both experiments, the threshold for early paired pulse depression (20 ms interpulse interval, IPI) was reached with moderate stimulation (30-40% of maximum). Above threshold, the test PS was depressed to a relatively constant amplitude in Experiment 1, in contrast to a nearly linear decrease observed in Experiment 2 with increasing strength of early paired pulse, relative to the conditioning reflects the lower stimulus intensity of the test pulse, relative to the conditioning pulse, in the second study, thereby allowing the increasing strength of early paired pulse depression to be detected more easily. The threshold for late paired pulse depression was reached near (20%, Experiment 1) or below (5%, Experiment 2) the PS threshold of dentate granule cells, and a paradoxical decrease in late paired pulse depression was detected with maximal stimulation in both studies. Together, these results suggest that early paired pulse depression exhibits a strong dependence upon the amplitude of the conditioning PS, whereas late paired pulse depression is marginally affected by the conditioning PS amplitude and is influenced by additional processes at both extremes of the stimulus intensity continuum.