[Abstract Title]. - Society for Neuroscience

NIMH
Title: The transition to hyperexcitability in stellate cells (SCs) from layer II of the medial
entorhinal cortex during temporal lobe epilepsy: A modeling study
Authors: *H. G. ROTSTEIN 1 , T. KISPERSKY 2 , J. A. WHITE 3 ;
1 Dept Math Sci., New Jersey Instit. Technol., Newark, NJ; 2 Program in Neurosci., Boston Univ.,
Boston, MA; 3 Dept. of Bioengineering, Univ. of Utah, Salt Lake City, UT
Abstract: Previous studies have shown that stellate cells (SCs) are hyperexcitable in animal
models of temporal lobe epilepsy. A recent 'in vitro' study using pilocarpine-treated rats (Kumar
et al. 2007) found evidence for the existence of recurrent excitatory connections among SCs,
reduced recurrent inhibition among SCs in epileptic animals and no change in recurrent
excitation. In this work we investigate the biophysical mechanism that governs the transition
from normal to hyperexcitable spiking activity in SCs. We use biophysical (conductance based)
modeling, simulations, dynamical systems techniques and dynamic clamp experiments. The SC
model includes a persistent sodium, an h- and an M- currents. We show that a minimal network
model including SCs and interneurons is able to qualitatively reproduce the experimental
findings. This model displays an abrupt transition between the two frequency regimes as the
result of small changes in the amount of inhibition. This abrupt transition also occurs in the
absence of inhibition, as a result of small changes in the amount of recurrent excitation. To
further investigate the biophysical mechanism that governs these phenomena we considered a
single SC connected to itself via an autapse. This approximation mimics the network activity and
is justified since SCs synchronize in phase and slightly out of phase in the theta and
hyperexcitable regimes respectively. We show that the abrupt changes in firing frequency can be
induced by increasing the amount of autaptic conductance, but not by increasing the level of the
applied (tonic) current in an isolated SC; i.e., they are the result of phasic but not tonic
excitation. 'In vitro' experimental resuts using a single, isolated SC and dynamic clamp to
generate an autapse confirmed our theoretical predictions. Our results show that a single, isolated
SCs have intrinsic dynamic properties that endow them with the potential ability to evolve on
both fast and slow time scales, and that the combination of excitatory and inhibitory network
properties determines the SC's frequency regime.
Disclosures: H.G. Rotstein, None; T. Kispersky, None; J.A. White, None.
Poster
250. Epilepsy: Networks
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 250.12/V24