Abstracts

The participation of the insular cortex (IC) in temporal lobe epilepsy (TLE) has long been suggested from studies of human epileptic patients; however, its network interactions with the perirhinal cortex (PC) and hippocampus remain uninvestigated. Here, we used a hippocampus-parahippocampus-IC rat brain slice to provide the first characterization of network epileptiform interactions among these structures during application of the convulsant 4-aminopyridine (4-AP)., Brain slices (450[micro]m) were prepared from adult male Sprague-Dawley rats. Field potential recordings were acquired using ACSF-filled glass electrodes positioned within area CA3 of the hippocampus, the PC and the IC. 4-AP (50[micro]M) was bath applied to induce epileptiform synchronous network activity., 4-AP induced three types of epileptiform activity: (i) fast interictal events (duration= 0.1-0.2 s; interval of occurrence= 0.7-1.2 s) that were mainly observed in CA3 as well as (ii) slow interictal (duration= 0.5-2.0 s; interval of occurrence= 4.0-21.7 s) and (iii) prolonged ictal-like (duration= 11.3-48.7 s; interval of occurrence= 17.9-332 s) that occurred synchronously among the PC and the IC and occasionally entered the hippocampus. Only slow interictal discharges were present in PC and IC in 15/30 slices. Moreover, slow interictal and ictal events were generated by the IC following surgical isolation. Ictal discharges were abolished by NMDA receptor antagonism while interictal activity persisted. Further antagonism of non-NMDA glutamatergic receptors abolished interictal discharges and disclosed slow field potentials that recurred at intervals of 11.4-28.0 s in all structures. Bath application of the [micro]-opioid receptor agonist [D-Ala²,N-Me-Phe⁴-,Gly-ol⁵]enkephalin (DAGO, 10[micro]M) significantly reduced the occurrence of these slow potentials in all structures (n=5); this effect was reversible with naloxone methiodide (20[micro]M). Application of the GABA[sub]A[/sub] receptor antagonist picrotoxin (50[micro]M) abolished these field potentials., Our results demonstrate that epileptiform activity occurs synchronously among PC and IC networks, while analogous activity can be generated independently within the isolated IC. These observations suggest that the network characteristics necessary and sufficient to initiate epileptiform network events are present within the IC., (Supported by: Funded by CIHR (Grant 8109), CURE and the Savoy Foundation.)