Abstracts

RATIONALE: Clinical and epidemiological observations have suggested that seizures in early life may not have significant long-term consequences. Recent experimental studies, however, have demonstrated that seizures during the postnatal period (P1-P14) in rats induced long-term deficits in synaptic plasticity (LTP)and hippocampal learning, which were associated with enhancement in the strength of GABAergic circuitry in the absence of overt seizure-induced neural damage (Lynch et al.,Eur.J.Neurosci., 2000; Soc. Neurosci. Abstr., 2000). To further assess long-term cognitive and behavioral effects of early postnatal seizures, adult rats (~P95)that experienced seizures during P1-P24 were compared to age-matched controls in terms of open field activity, activity in an elevated plus maze, and performance in a short-term radial arm maze task requiring hippocampal memory. METHODS: Seizures were induced in postnatal rats (P1-P24) by kainic acid (KA)at doses adjusted for age, and saline-injected littermates were controls. These rats were evaluated in adulthood (~P95) by measuring open field locomotor activity, activity in an elevated plus maze (time spent in covered/uncovered arms), and performance in an 8 arm radial maze during trials at 30 minute intervals. RESULTS: Adult rats that experienced seizures during P1-P24 demonstrated abnormalities in the elevated plus maze (increased preference for covered arms, a measure of avoidance/anxiety), impairments in radial arm maze performance (reduced rate of learning in a spatial memory task that is disrupted by hippocampal abnormalities), but no alteration in locomotor activity. Impairments were observed in all groups that experienced seizures on P1,P7,P14, or P24. CONCLUSIONS: Postnatal seizures in rats induce long-term cognitive and behavioral effects in tasks involving not only hippocampus, but also potentially other limbic and extra-limbic systems. These results, and previous observations demonstrating a long-term impairment in hippocampal LTP after postnatal seizures, demonstrate that seizures in early life alter postnatal development of neural circuitry with functional consequences that may not be benign.