CHANGES IN DENTATE GRANULE CELL FIELD POTENTIALS DURING AFTERDISCHARGE INITIATION TRIGGERED BY 5 HZ PERFORANT PATH STIMULATION

A failure of early paired pulse depression often precedes the onset of intermittent spontaneous seizures in animal models of status epilepti cus. In the present study, changes in the strength of early and late p aired pulse depression of dentate granule cell field potentials were c ompared in the unanesthetized rat during the initiation of a single af terdischarge (AD) evoked by perforant path stimulation (0.1 ms pulse d uration, 5 Hz: 12-18 s duration, 50-1000 mu A), Late paired pulse depr ession was measured by sequential changes in the population spike (PS) amplitude during 5 Hz stimulation (200 ms interpulse interval, IPI). When 5 Hz stimulation triggered an AD, the population spike (PS) was i nitially depressed and then increased to above pre-train values, indic ating a loss of late paired pulse depression by the middle of the trai n. Early paired pulse depression was measured by inserting paired puls es (20 ms IPI) at spaced intervals throughout the 5 Hz train. In contr ast to late paired pulse depression, early paired pulse depression rem ained at maximum strength until an abrupt failure was detected coincid ent with AD initiation. Two experimental treatments shown to increase the strength of late paired pulse depression, administration of the N- methyl-D-aspartate antagonist, MK-801 (0.25 mg/kg, i.p.), and the deve lopment of kindled seizures, produced an increase in AD thresholds and in the initial depression in the PS amplitude during 5 Hz stimulation . Together, these results suggest that a failure of late paired pulse depression may be a precipitating event in AD initiation triggered by 5 Hz stimulation in the unanesthetized rat.