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Volume 16, Number 14,
Issue of July 15, 1996
pp. 4438-4448
Copyright ©1996 Society for Neuroscience
Electrographic Seizures and New Recurrent Excitatory Circuits in
the Dentate Gyrus of Hippocampal Slices from Kainate-Treated Epileptic
Rats
Received Feb. 2, 1996; revised April 22, 1996; accepted April 26, 1996.
Jean-Pierre Wuarin and
F. Edward Dudek
Department of Anatomy and Neurobiology, Colorado State University,
Fort Collins, Colorado 80523
Mossy fiber sprouting has been proposed to lead to new excitatory
connections between dentate granule cells, which in turn cause
electrographic seizures. We tested this hypothesis in hippocampal
slices from rats made epileptic by kainate injections. The Timm's
histological method revealed intense staining of the inner molecular
layer in slices from all kainate-treated rats. In bicuculline (10 µM) and 6 mM
[K+]o, antidromic
stimulation of the granule cells evoked bursts of population spikes
superimposed on long-lasting negative shifts in all slices tested from
all kainate-treated rats. Long-duration (2-47 sec), seizure-like
bursts with tonic and clonic components occurred spontaneously (53%)
or in response to antidromic stimulation (81%). Under identical
conditions, prolonged bursts were never seen in slices from controls or
from kainate-injected rats 2-4 d after treatment. Glutamate microdrops
applied in the granule cell layer evoked abrupt increases in the
frequency of excitatory postsynaptic potentials (EPSPs) in two thirds
of the cells tested. Glutamate microstimulation was effective at
several sites in the granule cell layer but ineffective in the hilus.
The proportion of granule cells responding to local application of
glutamate by an increase in EPSPs was higher in slices with long bursts
(80% with bursts of >3 sec) than in slices with shorter bursts (33%
with bursts of <3 sec). Glutamate microstimulation did not affect
EPSPs in granule cells from control preparations. These results support
the hypothesis that kainate-induced mossy fiber sprouting forms new
excitatory connections between granule cells and can lead to increased
seizure susceptibility in the dentate gyrus.
Key words:
epilepsy;
hippocampus;
granule cell;
kainic
acid;
mossy fibers;
sprouting;
seizure-like bursting;
glutamate
microstimulation
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