Author: Muthumeenakshi Subramanian
Advisor: Dominique Durand
Location: Wickenden 321
Neural signals are primarily transmitted from one neuron to another through chemical and electrical synapses. We have studied another mechanism through which groups of orderly arranged neurons can communicate with other groups by endogenous electric fields independent of synaptic transmission. Large electric fields have been well documented particularly in epilepsy characterized by highly synchronized activity. We hypothesized that this electric field associated with the epileptic event can be used to control the generation and propagation of the spikes and seizures.
In this study, induced epileptic activity was induced by 4-Aminopyridine in hippocampal and cortical slices as well as in the hippocampus in in-vivo experiments. Two recording electrodes were used to record the activity in the slices. Four recording electrodes along the longitudinal axis was used for these acute in-vivo experiments. Two recording electrodes and two stimulating electrodes were used for controlling the electric field using an extracellular voltage clamp.
Induced activity propagated by electric field coupling across a physical cut in hippocampal and cortical slices. Theta waves, epileptic interictal spikes, and seizure like events also propagated across a physical cut or transection in the hippocampus in in-vivo experiments at a speed about 0.1 m/s characteristic of electric field coupling mediated propagation. The interictal spikes when analyzed for parameters differentiating spikes that make through the cut to the electrodes on the other side of the transection showed that sharp high amplitude spikes have a higher probability of propagating than smaller wider spikes. The feedback system using the extracellular voltage clamp suppressed 100% of the spikes and seizures induced.
Electric fields play an important role in the generation and propagation of epileptic events even through a transection in the tissue. We have successfully used the endogenous field to control the induction of epileptic events at the focus. The spatial extent of this control is unknown; however, the clamp is shown to be effective when applied to a small known focus.