Abstract
Focal seizure propagation is classically thought to be spatially contiguous. However, propagation through the epileptic network – a collection of disparate epileptic nodes - has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts were limited to a 2-3 mm region without clear propagation, they were associated with hemisphere-wide LFP fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. Globally compromising this inhibitory response using bicuculline surface application resulted in classical contiguous propagation; whereas, focal bicuculline microinjection resulted in epileptic network formation with two physically disparate foci. Our study suggests both classical and epileptic network propagation could arise from inhibition defects without pre-existing pathological connectivity changes, and that preferred propagation pathways may result from variations in cortical topology.