Abstract Details

Presented By: Kispersky, Tilman
Affiliated with: Boston University, Neuroscience
Authors: Kispersky T, White JA, Rotstein H
From: Boston Universiy, University of Utah, New Jersey Institute of Technology
Title
The role of Kv7 mediated potassium currents and recurrent excitation in stellate cells of the entorhinal cortex in a dynamic clamp based model of temporal lobe epilepsy
Abstract

Recent experimental work has suggested that the epileptic state in the temporal lobe of the rat brain is

associated with a decrease in recurrent inhibition but no change in excitation. In modeling work we

have explored the generation of epileptic-like behaviors in networks without inhibition and find that

once recurrent excitation reaches a threshold level, sustained, high frequency firing is induced. These

networks synchronize slightly out of phase so they can be approximated by single stellate cells

connected via an autapse. To study this phenomenon in vitro we used slices of rat entorhinal cortex and

dynamic clamp to couple single stellate cells to themselves to mimic such recurrent excitation. We find

that autaptic coupling, at a threshold level of conductance, does indeed cause a sudden transition to an

epileptic-like state. Unlike the computational model, which lacks slow potassium currents known not

to contribute to subthreshold oscillations, the in vitro model does not sustain firing but instead enters

into a bursting regime in which periods of high frequency firing are interspersed by periods of

quiescence. To understand the biophysical mechanisms underlying this behavior we investigated the

role of the Kv7 mediated potassium current (m-current) since its introduction into the model caused

bursting behavior similar to that seen in vitro. We find that pharmacologically blocking the m-current

with linopirdine in recurrently connected stellate cells causes an increase in burst duration but not a

change in the interspike interval (ISI) during bursts. In control conditions, the slow buildup of

adaptation mechanisms including the m-current lead to the termination of a burst after a few spikes. As

supported by our theoretical studies, we hypothesize that m-current block attenuates these adaptation

mechanisms and thus permits longer periods of burst firing. We conclude that recurrent excitation is

sufficient to induce epileptic-like behavior in single stellate cells and that this behavior is modulated by

the presence of the m-current.