PHARMACOLOGICAL PROPERTIES OF EPILEPTIFORM SYNCHRONIZATION IN AMYGDALA/ENTORHINAL CORTEX NETWORKS [italic]IN VITRO[/italic]
Abstract number :
2.001
Submission category :
Year :
2002
Submission ID :
3491
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Ruba Benini, Margherita D[ssquote]Antuono, Massimo Avoli. Dept. Neurology & Neurosurgery, and Physiology, Montreal Neurological Institute/McGill University, Montreal, Quebec, Canada; IRCCS Neuromed, Pozzilli, (Isernia), Italy
RATIONALE: The amygdala is involved in some of the behavioral manifestations observed during seizures in temporal lobe epilepsy patients where it is often a primary focus of seizure activity. Here we used horizontal rat brain slices maintained [dsquote]in vitro[dsquote] to understand its involvement in epileptiform synchronization.
METHODS: Field potential and sharp-electrode intracellular recordings were obtained from rat brain slices that included the hippocampus, a portion of the basolateral/lateral nuclei of the amyg-dala (BLA) and the entorhinal cortex (EC) during bath application of the con-vulsant drug 4-aminopyridine (4AP, 50[mu]M).
RESULTS: CA3-driven interictal discharges occurred in all structures at intervals of 1.2-2.8s during 4AP application. These discharges had duration of 310[plusminus]40ms (n=14) when measured in CA3, spread to the EC and BLA, and were abolished in these parahippocampal areas by cutting the Schaffer collaterals. This procedure induced the appearance of ictal (duration[gt]10s) discharges along with slower interictal events that originated in either EC or BLA. In intact slices, the specific NMDA antagonist CPP increased the rate of occurrence and decreased the duration of CA3-driven interictal discharges in all areas. Moreover, the effects of CPP were not seen in CA3 when it was isolated from the EC/BLA. In Schaffer collateral lesioned slices, CPP abolished ictal discharges and reduced the duration of the slow interictal activity recorded in EC and BLA; moreover application of the GABA[sub]A[/sub] receptor antagonist picrotoxin to Schaffer collateral lesioned slices made ictal discharges disappear and be replaced by a continuous pattern of robust interictal activity.
CONCLUSIONS: In the presence of 4AP, CA3 outputs entrain EC and BLA networks into a pattern of interictal activity that inhibits the occurrence of NMDA receptor-dependent ictal discharges resembling electrographic limbic seizures. Moreover, occurrence of these ictal events in BLA and EC require the function of GABA[sub]A[/sub] receptor-mediated mechanisms.
[Supported by: Canadian Institutes of Health Research and Savoy Foundation.]