CA3-released entorhinal seizures disclose dentate gyrus epileptogenicity and unmask a temporoammonic pathway.
We have investigated the propagation of epileptiform discharges induced by 4-aminopyridine (4-AP, 50 microM) in adult mouse hippocampus-entorhinal cortex slices, before and after Schaffer collateral cut. 4-AP application induced 1) ictal epileptiform activity that disappeared over time and 2) 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 12 mM from a baseline value of 3.2 mM), whereas smaller rises in [K(+)](o) (up to 6 mM) 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 with 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.
Barbarosie
M
M
Departments of Neurology and Neurosurgery, and Physiology, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
Louvel
J
J
Kurcewicz
I
I
Avoli
M
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology*; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008839:Microelectrodes; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D015761:4-Aminopyridine; D011188:Potassium