Ca3-Released Entorhinal Seizures Disclose Dentate Gyrus Epileptogenicity And Unmask A Temporoammonic Pathway. Michaela Barbarosie1, Jacques Louvel2, Irčne Kurcewicz2 and Massimo Avoli1. 1Montreal Neurological Institute, Departments of Neurology and Neurosurgery, and Physiology, McGill University, Montreal, QC, H3A 2B4, Canada, and 2Centre Paul Broca and INSERM U109, 75014 Paris, France.
APStracts 6:0542N, 1999.
We have investigated the propagation of epileptiform discharges induced by 4-aminopyridine (4AP, 50µM) in adult mouse hippocampus-entorhinal cortex slices, before and after Schaffer collateral cut. 4AP application induced: (i) ictal epileptiform activity that disappeared over time, and (ii) interictal epileptiform discharges, which continued throughout the experiment. Using simultaneous field potential and [K+]o recordings, we found that entorhinal and dentate ictal epileptiform discharges were accompanied by comparable elevations in [K+]o (up to 12mM from a baseline value of 3.2mM), while smaller rises in [K+]o (up to 6mM) were associated with ictal activity in CA3. Cutting the Schaffer collaterals disclosed the occurrence of ictal discharges that were associated with larger rises in [K+]o as compared to the intact slice. Further lesion of the perforant path blocked ictal activity and the associated [K+]o increases in the dentate gyrus, indicating synaptic propagation to this area. Time delay measurements demonstrated that ictal epileptiform activity in the intact hippocampal-entorhinal cortex slice, propagated via the trisynaptic path. However, after Schaffer collateral cut, ictal discharges continued to occur in CA1 and subiculum, and spread to these areas directly from the entorhinal cortex. Thus, our data indicate that the increased epileptogenicity of the dentate gyrus (a prominent feature of temporal lobe epilepsy as well), may depend on perforant path propagation of entorhinal ictal discharges, irrespective of mossy fiber reorganization. Moreover, hippocampal neuronal damage that is acutely mimicked in our model by Schaffer collateral cut, may contribute to "short-circuit" propagation of activity by pathways that are masked when the hippocampus is intact.
Received 21 May 1999; accepted in final form 25 October 1999.
APS Manuscript Number J420-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999