[Abstract Title]. - Society for Neuroscience

Authors: *T. J. KISPERSKY 1 , J. A. WHITE 2 , H. G. ROTSTEIN 3 ;
1 Program Neurosci, Boston Univ., Boston, MA; 2 Dept. of Bioengineering, Univ. of Utah, Salt
Lake City, UT; 3 Dept. of Mathematical Sci., New Jersey Inst. of Technol., Newark, NJ
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.
Disclosures: T.J. Kispersky , None; H.G. Rotstein, None; J.A. White, None.
Poster
250. Epilepsy: Networks
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 250.11/V23
Topic: B.09.d. Oscillations and synchrony: Other
Support: NIMH
NINDS