Tetraethylammonium-induced epileptiform activity in young and adult rat hippocampus

Abstract

Extracellular field potential recordings were used to study the epileptiform activity evoked by tetraethylammonium (TEA) in the CA3 subfield of hippocampal slices obtained from young (12–18 day-old) and adult (>60-day-old) rats. During TEA application (5–10 mM), young slices generated both ictal-like (duration: up to 28 s, rate of occurrence 1–3 × 10⁻² s⁻¹) and interictal-like (duration: 1.5–2 s; rate of occurrence: 1–3 × 10⁻¹ s⁻¹) activity. In adult slices only interictal-like activity was induced by TEA (3–10 mM). Depending on the concentrations of TEA, these events lasted 80–600 ms and occurred at 5–60 × 10⁻² s⁻¹. Both the $\text{N-}\text{methyl-}\text{d}\text{-aspartate}$ (NMDA) receptor antagonist 3-3(2-carboxypiperazine-4-yl)propyl-1-phosphonate (5–10 μM; CPP) and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (5–10 μM; CNQX) were necessary to suppress ictal-likeand interictal-like discharges in young slices. By contrast, interictal-like activity in adult slices was reduced and eventually blocked by CNQX (0.5–3 μM) alone. Furthermore the pattern of epileptiform discharges seen in young slices was modified by CPP (i.e. decrease in the rate of occurrence of ictal events and reduction in the duration of interictal discharges), while the activity recorded in adult slices was resistant to this NMDA antagonist. Bicuculline methiodide (5 μM; BMI) enhanced the duration of epileptiform activities in both young and adult slices. Our data demonstrate that the epileptiform discharges induced by TEA in the CA3 subfield of the rat hippocampus display age-dependent patterns of activity. Furthermore, the participation of non-NMDA and NMDA receptors in TEA-induced epileptiform discharges undergo changes during brain maturation. Finally, the effects induced by BMI indicate a modulatory role for GABA_A-receptor-mediated mechanisms in both young and adult hippocampus treated with TEA.