Abstracts

Rationale: In the 4-aminopyridine (4-AP) model of in vitro seizures, neurons exhibit spontaneous interictal bursts and prolonged repetitive ictal-like discharges (Ziburkus et al., 2006). It is well established that the epileptic neuronal networks learn and accordingly change the efficacy of synaptic signaling and connectivity. However, little is known about how short-term changes in synaptic plasticity transform the patterns of epileptic signal propagation. Methods: Using simultaneous electrophysiology (extracellular and whole-cell recordings) and fast (up to 1 KHz) voltage-sensitive dye (Di-4ANNEPS) imaging (MiCam CCD system) we describe changes in short-term plasticity (STP) and the dynamics of pattern formation during the stimulus trains and spontaneous interictal bursts in juvenile (P20-P30) rat brain slices. Two types of slices were used in the experiments, transverse hippocampal slices and tangential somatosensory and visual cortical slices. Results: In transverse hippocampal slices, stimulation of the Schaffer collaterals in the CA3 using varied frequency trains (20Hz, 50Hz and 100Hz; 10 stimuli of 0.2ms duration) evoked either facilitating or depressing field and whole-cell excitatory postsynaptic potentials (EPSPs, n=12) in the CA1 area. Fast optical imaging could resolve single half-maximal amplitude evoked EPSPs (even during 100Hz stimulus trains) and spontaneous interictal bursts. Frequency-dependent changes in STP produced different kinetics and evolution patterns of the waveforms in control and 4-AP (200 μM) treated slices. In control, the propagating waves in hippocampus were confined to a small area of the Schaffer collateral projections. In contrast, in the 4-AP treated slices the wave propagation patterns were less specific and continuous residual depolarization could be observed during the high frequency (>20Hz) stimulus trains. The same studies were also conducted in tangential somatosensory and visual cortical slices (n=15). In tangential slices, the stimulated EPSP and spontaneously arising interictal wave dynamics were diverse and exhibited complex multidirectional propagation patterns. Spontaneously propagating waves in both hippocampal and neocortical slices often demonstrated rhythmic oscillations between hyperpolarization and depolarization. Conclusions: These studies provide possible mechanisms by which frequency-dependent plastic epileptic networks alter the normal neuronal wave propagation dynamics.