Abstracts

RATIONALE: Evidence for the role of non-synaptic mechanisms in the synchronization of seizure discharges comes from in vitro models of epileptiform activity produced in the absence of calcium. Here, we tested whether seizure-like discharges could occur in the presence of normal levels of extracellular calcium. METHODS: Hippocampal slices were prepared by conventional techniques and incubated in high potassium (12mM), cesium (5mM), 4-AP (50mM) or TEA (5mM) until spontaneous interictal activity was recorded in CA1 and CA3. Synaptic transmission was then blocked by the addition of neurotransmitter blockers (CNQX 20mM, AP-V 100mM and bicuculline 20mM) or addition of the calcium channel blocker cadmium (200mM). RESULTS: Increasing excitability by perfusion with 12 mM potassium resulted in spontaneous interictal discharges in CA1 and CA3 within 30 minutes. Addition of either neurotransmitter blockers or cadmium blocked the interictal discharges within 15-20 minutes and with continued perfusion (with synaptic transmission blocked) field bursts (seizure-like activity) appeared in CA1 in 33-40% of slices and in the dentate gyrus in 30% of slices. Field bursts were rarely recorded in CA3. Similar results were obtained when the epileptiform activity was induced with the potassium channel blockers 4-AP, TEA or cesium, except that field bursts were detected in CA3 in addition to CA1 and the dentate gyrus after blockade of synaptic transmission. Interictal discharges were also induced by modulation of synaptic transmission using a 0-added magnesium perfusing solution. In this case blocking synaptic tranmission stopped the interictal activity, but did not induce field bursts in any area. CONCLUSIONS: These experiments show that non-synaptic mechanisms can synchronize neuronal activity in the presence of normal levels of extracellular calcium. Initiation of the prolonged field bursts appears to require an increase in neuronal excitability plus blockade of synaptic transmission. In contrast, interictal activity can be induced by increasing neuronal excitability a variety of ways.