A nonsynaptic mechanism underlying interictal discharges in human epileptic neocortex

Abstract

Very fast oscillations (VFOs, >80 Hz) are important for physiological brain processes and, in excess, with certain epilepsies. Putative mechanisms for VFO include interneuron spiking and network activity in coupled pyramidal cell axons. It is not known whether either, or both, of these apply in pathophysiological conditions. Spontaneously occurring interictal discharges occur in human tissue in vitro, resected from neocortical epileptic foci. VFO associated with these discharges was manifest in both field potential and, with phase delay, in excitatory synaptic inputs to fast spiking interneurons. Recruitment of somatic pyramidal cell and interneuron spiking was low, with no correlation between VFO power and synaptic inputs to principal cells. Reducing synaptic inhibition failed to affect VFO occurrence, but they were abolished by reduced gap junction conductance. These data suggest a lack of a causal role for interneurons, and favor a nonsynaptic pyramidal cell network origin for VFO in epileptic human neocortex.