Neuronal aggregate formation underlies spatiotemporal dynamics of nonsynaptic seizure initiation

Abstract

High-frequency activity often precedes seizure onset. We found that electrographic seizures, induced in vitro using the low-Ca(2+) model, start with high-frequency (>150 Hz) activity that then decreases in frequency while increasing in amplitude. Multichannel and unit recordings showed that the mechanism of this transition was the progressive formation of larger neuronal aggregates. Thus the apparent high-frequency activity, at seizure onset, can reflect the simultaneous recording of several slower firing aggregates. Aggregate formation rate can be accelerated by reducing osmolarity. Because synaptic transmission is blocked when extracellular Ca(2+) is reduced, nonsynaptic mechanisms (gap junctions, field effects) must be sufficient for aggregate formation and recruitment.