4th Annual Mountain West
Biomedical Engineering Conference
September 5-6, 2008
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
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.