Epileptiform Activity in the Dentate Gyrus During Low Calcium Perfusion and
Exposure to Transient Electric Fields.
Richardson, Thomas L., and Collette N. O'Reilly.
School of Kinesiology, Simon Fraser University, Burnaby, British Columbia,
Canada, V5A 1S6.
APStracts 2:0034N, 1995.
SUMMARY AND CONCLUSIONS
1) The dentate gyrus fails to develop epileptiform activity in many
experimental models of epilepsy including the in vitro low-Ca 2+ model.
Although manipulating the [K + ] or osmolality of normal low-Ca 2+
perfusion mediums can enhance the propensity of the dentate gyrus to develop
seizure activity, the specific mechanisms contributing to this change are
still under investigation. Identification of these mechanisms should improve
our understanding of epileptogenesis and of the factors contributing to the
propensity for seizure discharge in other tissues. 2) The present experiments
used externally generated electric fields to depolarize the somata of large
populations of dentate granule cells during exposure to a perfusion medium
with no added Ca 2+ (low-Ca 2+ ). Uniform electric fields were generated
across an individual slice by passing current between two parallel AgCl coated
silver wires placed on the surface of the ACSF. The wires were positioned to
straddle the slice such that the current flow was parallel to the dendro-
somatic axis of the cell population under investigation. 3) Under control
conditions (low-Ca 2+ medium, no applied field) stimulation of the dentate
hilus evoked a single antidromic population spike in 89% of the slices studied
(n=27). During application of electric fields the same stimulus evoked
epileptiform activity in all trials. Well-formed bursts first occurred at an
average field intensity of +22.9 +/- 2.5 mV/mm (n=24). The amplitude of
individual spikes and the total number of spikes within a burst increased in a
graded fashion as the magnitude of the applied field was increased. 4) High
field intensities evoked epileptiform activity in the absence of a
synchronizing antidromic stimulus. These field-induced bursts occurred
following a progressive build up of rhythmical activity recorded in the extra-
somatic space and could persist for the entire duration of an applied field
lasting for several seconds. The average field intensity required to produce a
threshold burst was +84.6 +/- 3.6 mV/mm (n=24). 5) In 11% of trials (3/27) the
dentate gyrus exhibited poorly developed antidromic bursting without the
application of depolarizing electric fields. These bursts were completely
suppressed by hyperpolarizing fields in the range of -10 to -20 mV/mm. 6) The
results of this investigation support the hypothesis that granule cell
sensitivity to non-synaptic interactions is adequate to support bursting in a
normal low-Ca 2+ medium, but bursting fails to occur because these cells are
normally too hyperpolarized relative to their action potential threshold. The
results also confirm that the sensitivity of granule and pyramidal cells to
field effects and other forms of non-synaptic interactions is adequate to
support epileptic activity despite the fact that these cells differ with
respect to neuronal morphology, anatomical organization, and
electrophysiological characteristics.
Received 18 October 1994; accepted in final form 1 March 1995.
APS Manuscript Number J648-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 3 April 1995.