Abstracts

Propagating epileptiform activity waves in disinhibited neocortical slices have been used as a model for seizure propagation. In theoretical models of wave propagation in cortex, it has been predicted that propagation speed is dependant on neuronal firing threshold. Since applied electric fields can polarize neurons and thereby control threshold, we hypothesized that such fields could be used to control and block seizure propagation.
Male Sprague-Dawley rats age p26-p68 were anesthetized with diethyl-ether and decapitated. Brains were removed and 400[mu]m thick neocortical slices from S1 were cut with a vibrotome. Slices were placed in an interface chamber and perfused with artificial cerebrospinal fluid containing 5-8.3[mu]M picrotoxin at 34[deg]C. A bipolar stimulation electrode was placed in layer 5 at one end of the slice to initiate epileptiform bursts that propagate parallel to the pial surface. Double barreled glass micropipette electrodes filled with 0.9% NaCl were used to differentially record local extracellular field activity in layers 2/3 both near and far from the stimulation site. A uniform electric field was generated with Ag/AgCl electrodes embedded in the chamber floor. Slices were aligned such that fields were applied perpendicular to the pial surface of the slice, i.e. perpendicular to direction of propagation and parallel to the somato-dendritic axes of the pyramidal cells. Propagation velocity was studied as a function of field amplitude and polarity.
In all 25 slices tested with stable wave initiation, modulation of propagation speed was observed. Positive fields applied to the pial surface (in the direction from layer 1 to layer 6) increased and negative fields decreased the speed of propagation. Propagation could be blocked with sufficiently high negative field amplitudes.
We experimentally demonstrated that electric fields can be used to modulate the speed of propagation of epileptiform activity in cortex. At sufficient field intensities propagation can be blocked. We propose that localized electric fields could be used to hinder or halt the spread of epileptiform activity in cortex during seizures.
[Supported by: Biomedical Engineering Research Grant from the Whitaker Foundation RG990432; National Institutes of Health grants K02MH01493 and R01MH50006]