Abstracts

Rationale: Early childhood epilepsy is often associated with significant cognitive impairment. However the mechanisms for this impairment remain uncertain and it is not clear to what extent early onset seizures, underlying structural abnormalities or interictal epileptiform abnormalities are responsible. Methods: We studied the maturation of hippocampal function in normal rats and in a rat model of malformation in cortical development -MAM (Methyl-Asoxy-Methanol injections at gestational day 17) in which half the animals had 50 neonatal seizures induced by flourothyl - MNS). Hippocampal function was assessed using single unit recordings of place cells (pyramidal neurons characterized by their location-specific firing). These cells are believed to provide a neurological substrate for spatial representation and memory. In adult animals, place cell firing provides strong location information and is identical at each new introduction to the same environment. Results: Normal immature rats have noisy and unstable place cell representation that progressively develops to reach a pattern comparable to adults, first identified at P35. In contrast there were very few functional place cells in MAM and/or MNS immature animals. Adult recordings of both groups are currently underway. No interictal discharges were seen in any animal Conclusions: Both MAM and MNS rats have abnormal electrophysiological development of hippocampus which could underlie cognitive impairment. The additional impact of neonatal seizures on cognition in animals with a structural abnormality requires further study.