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The Journal of Neurophysiology Vol. 85 No. 3 March 2001, pp. 1067-1077
Copyright ©2001 by the American Physiological Society
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523
Wuarin, Jean-Pierre and
F. Edward Dudek.
Excitatory Synaptic Input to Granule Cells Increases With
Time After Kainate Treatment. J. Neurophysiol. 85: 1067-1077, 2001. Temporal lobe epilepsy is usually
associated with a latent period and an increased seizure frequency
following a precipitating insult. After kainate treatment, the mossy
fibers of the dentate gyrus are hypothesized to form recurrent
excitatory circuits between granule cells, thus leading to a
progressive increase in the excitatory input to granule cells. Three
groups of animals were studied as a function of time after kainate
treatment: 1-2 wk, 2-4 wk, and 10-51 wk. All the animals studied
10-51 wk after kainate treatment were observed to have repetitive
spontaneous seizures. Whole cell patch-clamp recordings in hippocampal
slices showed that the amplitude and frequency of spontaneous
excitatory postsynaptic currents (EPSCs) in granule cells increased
with time after kainate treatment. This increased excitatory synaptic
input was correlated with the intensity of the Timm stain in the inner
molecular layer (IML). Flash photolysis of caged glutamate applied in
the granule cell layer evoked repetitive EPSCs in 10, 32, and 66% of
the granule cells at the different times after kainate treatment. When
inhibition was reduced with bicuculline, photostimulation of the
granule cell layer evoked epileptiform bursts of action potentials only in granule cells from rats 10-51 wk after kainate treatment. These data support the hypothesis that kainate-induced mossy fiber sprouting in the IML results in the progressive formation of aberrant excitatory connections between granule cells. They also suggest that the probability of occurrence of electrographic seizures in the dentate gyrus increases with time after kainate treatment.
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