Paired pulse stimulation of the perforant path provides a measure of i
nhibition of dentate granule cell field potentials that is reflected i
n the depression of the second (test) population spike (PS) relative t
o the first (conditioning) PS. The assumption that the strength of pai
red pulse depression is dependent upon the amplitude of the conditioni
ng PS was investigated by increasing the stimulus intensity of both pu
lses (5-100% of maximum, Experiment 1), or by increasing the stimulus
intensity of the conditioning pulse (5-100%) while maintaining a const
ant stimulus intensity of the test pulse (50%, Experiment 2). In both
experiments, the threshold for early paired pulse depression (20 ms in
terpulse interval, IPI) was reached with moderate stimulation (30-40%
of maximum). Above threshold, the test PS was depressed to a relativel
y constant amplitude in Experiment 1, in contrast to a nearly linear d
ecrease observed in Experiment 2 with increasing stimulus intensity. T
his difference most likely reflects the lower stimulus intensity of th
e test pulse, relative to the conditioning pulse, in the second study,
thereby allowing the increasing strength of early paired pulse depres
sion to be detected more easily. The threshold for late paired pulse d
epression was reached near (20%, Experiment 1) or below (5%, Experimen
t 2) the PS threshold of dentate granule cells, and a paradoxical decr
ease in late paired pulse depression was detected with maximal stimula
tion in both studies. Together, these results suggest that early paire
d pulse depression exhibits a strong dependence upon the amplitude of
the conditioning PS, whereas late paired pulse depression is marginall
y affected by the conditioning PS amplitude and is influenced by addit
ional processes at both extremes of the stimulus intensity continuum.