Effects of hippocampal kindling on paired-pulse response in CA1 in vitro.

Kindled rats were given high-frequency stimulations delivered to hippocampal CA1 on one side to induce afterdischarges (ADs). Control rats received the same number of pulses of a similar intensity at 0.17 Hz (low-frequency stimulations (LFSs)). On 1-2 days or on 21-23 days after fifteen ADs/LFSs (delivered hourly, 5 times a day over 3 days), hippocampal slices were prepared and incubated in vitro, with the experimenter blind to the previous history of stimulation of the rat. Extracellular responses following single or paired-pulse stimulation of the Schaffer collaterals (stratum radiatum) were recorded at the CA1 cell layer in vitro, and analyzed as population excitatory postsynaptic potentials (EPSPs) and population spikes. At 1.5, 2 or 4 times the response threshold, and on either day 1 or day 23 after the last AD/LFS, the paired-pulse response at interpulse intervals of 30-200 ms was significantly larger for the kindled group of slices than for the control group (ANOVA, typically P less than 0.0001), for either the population spike or the population EPSP. Stimulus thresholds for the evoked response did not differ between kindled and control group of slices. The population EPSP and spike in response to a single pulse were enhanced (as compared to the control group) on day 1 but not on day 23 after kindling. The facilitation of paired-pulse response may be interpreted as caused by a decrease in postsynaptic (and possibly presynaptic) inhibition in the hippocampal CA1 region, which persisted to at least 3 weeks after hippocampal kindling.