Developmental characteristics of epileptiform activity in immature rat neocortex: a comparison of four in vitro seizure models

New-onset seizures and epilepsy have a relatively high incidence in infants and children. A leading hypothesis to explain an increased seizure suscept ibility of the immature nervous system involves ontogenetic changes in diff erent neurotransmitter systems, such as specific glutamate and GABA recepto rs. However, few studies have directly tested this hypothesis in a systemat ic fashion, especially in neocortical structures, where seizures in pediatr ic patients frequently arise. The present study investigated developmental changes in epileptiform. activity in rat neocortical slices from four age g roups (postnatal days P4-7, P13-16, P23-26, P41-47) due to four pharmacolog ical conditions (4-aminopyridine, low magnesium, picrotoxin, CGP-35348) tha t differentially modulate glutamate and GABA systems. A characteristic age- dependence of the incidence of epileptiform activity was observed. In all p harmacological conditions, no epileptiform. activity occurred in neocortica l slices from P4-7 rats. Interictal discharges, ictal events, and spreading depression had a maximal incidence at P13-16 and decreased progressively i n later age groups. 4-Aminopyridine, low magnesium, and picrotoxin induced all types of epileptiform activity with a similar age-dependent pattern, de spite minor differences in quantitative characteristics of epileptiform act ivity between these three conditions. The GABA(B) antagonist, CGP-35348, di d not elicit epileptiform activity in any age group, but could potentiate s ynaptic potentials. These findings establish that isolated neocortical tiss ue intrinsically displays ontogenetic changes in seizure susceptibility ind ependent of systemic factors. The similar age-dependent patterns of epilept iform activity with multiple drugs support a concept of global developmenta l changes in excitability not specifically linked to any particular neurotr ansmitter system. (C) 2001 Elsevier Science BY All rights reserved.