Abnormal Dentate Gyrus Network Circuitry in Temporal Lobe Epilepsy

Robert S. Sloviter, Argyle V. Bumanglag, Robert Schwarcz and Michael Frotscher

in Jasper's Basic Mechanisms of the Epilepsies

Fourth edition

Published on behalf of ©Jeffrey L. Noebels, Massimo Avoli, Michael A. Rogawski, Richard W. Olsen, and Antonio V. Delgado-Escueta

Published in print July 2012 | ISBN: 9780199746545
Published online April 2013 | e-ISBN: 9780199322817 | DOI:

Series: Contemporary Neurology Series

Abnormal Dentate Gyrus Network Circuitry in Temporal Lobe Epilepsy

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The mechanisms that cause acquired temporal lobe epilepsy are unknown. Suspected mechanisms include neuron loss, synaptic reorganization, and granule cell dispersion, but determining which abnormalities mediate epileptogenesis has been problematic because the most frequently used chemoconvulsant-based animal models exhibit extreme variability and minimal evidence of hippocampal epileptogenesis. Continuous monitoring of behavior and granule cell layer activity in awake rats after hippocampal injury caused by stimulation-induced status epilepticus has now shown that granule cells generate spontaneous field depolarizations, population spikes, and epileptiform discharges in the first days post-injury, prior to each generalized behavioral seizure. Thus, injury-associated hippocampal epileptogenesis is coincident with initial neuron loss, not delayed secondary processes. We hypothesize that neuron loss in the entorhinal cortex disrupts the functional separation of Layer II “grid cells,” causing abnormal synchronous discharges that invade the dentate gyrus. This, in turn, produces population spikes and epileptiform discharges in granule cells disinhibited by injury-induced hilar neuron loss. Long delays between injury and generalized behavioral seizures, when they occur, may primarily involve a “kindling” process in which initially focal (subclinical) discharges gradually increase in duration and cause clinical seizures. Neuroprotection in the immediate post-injury period, and prolonged anti-kindling therapy, might be the most effective anti-epileptic strategy.

Chapter.  9651 words.  Illustrated.

Subjects: Neurology

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