Small changes in synaptic gain lead to seizure-like activity in neuronal network at criticality

Epilepsy is a neurological disorder characterised by spontaneous recurrent seizures. The mechanisms by which multiple molecular and cellular changes lead to seizures is not well understood. Here, we study cortical seizure generation by simulating the activity of neuron groups in a network using the laminar cortex model. We identified a clear boundary between low-amplitude, asynchronous activity and high-amplitude, rhythmic activity, around which small changes in excitatory synaptic gain led to strong oscillatory activity. Neuron groups only responded significantly to stimulation around the boundary. The consequences of biophysical changes induced by epilepsy-related SCN1A mutations were also examined. Marked reduction in neuronal inhibition, as caused by mutations underlying Dravet syndrome, invariably led to strong neuronal firing, whereas small reductions in inhibition could cause significant changes when the network was poised close to the boundary. The study highlights the critical role of network dynamics in seizure genesis.