Developmental features of 4-aminopyridine induced epileptogenesis

Abstract

4-Aminopyridine (4-AP, 50 μM), perfused in rat hippocampal slices from postnatal days 2–30 (P2–P30), induced in the CA3 area the appearance of spontaneous epileptiform discharges, short (interictal-like) and sustained (ictal-like), as well as a slow potential. The duration of epileptiform discharges decreased and their rate of occurrence (frequency) increased with maturation: their duration during the 1st postnatal week was 4–6 times longer and their frequency 5 times lower, compared to those of the 4th postnatal week. Ictal discharges gradually disappeared at the end of the 4th postnatal week. Spontaneous synchronous activity — as a whole — often appeared in clusters separated by equal or longer length inactive periods, during the first two postnatal weeks. At the same period, ictal discharges were often followed by repetitive afterdischarges, forming sequences which lasted 0.7–1.5 min. Sectioning experiments showed that epileptiform discharges were generated in CA3, and their presence in CA1 depended on the integrity of CA1-CA3 synaptic connections. In conclusion, these findings demonstrate that (i) immature CA3 can generate synchronous epileptiform discharges as early as P2, (ii) such discharges are longer lasting and more complex during the early developmental stages and (iii) there are two time points (end of 2nd, end of 4th postnatal weeks), when maturational changes alter the epileptogenic properties of immature hippocampus.