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 mu M) in adult mouse hippocampus-entorhinal corte x slices, before and after Schaffer collateral cut. 4-AP application induce d I) ictal epileptiform activity that disappeared over time and 2) interict al epileptiform discharges, which continued throughout the experiment. Usin g simultaneous field potential and [K+](o) recordings, we found that entorh inal and dentate ictal epileptiform discharges were accompanied by comparab le elevations in [K+](o) (up to 12 mM from a baseline value of 3.2 mM), whe reas smaller rises in [K+](o), (up to 6 mM) were associated with ictal acti vity in CA3. Cutting the Schaffer collaterals disclosed the occurrence of i ctal discharges that were associated with larger rises in [K+](o) as compar ed with the intact slice. Further lesion of the perforant path blocked icta l activity and the associated [K+](o) increases in the dentate gyms, indica ting synaptic propagation to this area. Time delay measurements demonstrate d that ictal epileptiform activity in the intact hippocampal-entorhinal cor tex slice propagated via the trisynaptic path. However, after Schaffer coll ateral cut, ictal discharges continued to occur in CA1 and subiculum and sp read to these areas directly from the entorhinal cortex. Thus our data indi cate that the increased epileptogenicity of the dentate gyrus (a prominent feature of temporal lobe epilepsy as well), may depend on perforant path pr opagation of entorhinal ictal discharges, irrespective of mossy fiber reorg anization. Moreover, hippocampal neuronal damage that is acutely mimicked i n our model by Schaffer collateral cut, may contribute to "short-circuit" p ropagation of activity by pathways that are masked when the hippocampus is intact.