Figure 4. Impact of IEDs on the transition to seizure.

(a) IEDs interfere with the slow process of transition to seizure and HFA. Raw data and the corresponding time-frequency plot demonstrate the suppression of HFA after each discharge. (b) Details of IEDs generated in the CA3 and propagating to the CA1. (c) The average phase histogram demonstrates that the probability of HFA occurrence substantially increases during the peak of the discharge. It is then followed by transient HFA suppression and then its gradual increase until the next IED (n=15 slices). (d) Post-discharge suppression of HFA persists throughout the course of entire period between seizures. (e) Periods between seizures in intact hippocampi (n=83/15 interictal periods/slice) have longer duration than in isolated CA1 preparations, where the IEDs are absent (n=114/17 interictal periods/slice; two-sided Mann-Whitney-Wilcoxon U test, U=1577, P=0.000). (f) Block of IEDs by NBQX and APV also shortens the interictal period (baseline recording: n=27/5 interictal periods/slices; post-NBQX+APV: 42/5 interictal periods/slices, two-sided Mann-Whitney-Wilcoxon U test, U=188, P=0.000). (g) IEDs modify the seizure initiation pattern. In isolated CA1 preparations, seizures are characterized by focal initiation and slow spread of seizure activity to the rest of the CA1. (h) In intact slices, seizures initiate instantaneously across large areas or the entire CA1 due to incoming IEDs from the CA3. (i) Cumulative histogram of the seizure spread velocity in the intact hippocampus and isolated CA1 slices demonstrates that the seizure spreads by nearly two orders faster than in the intact slice. P<0.001 (***). Line and error bars represent mean and s.e.m respectively; ***P ≤ 0.001.