title: Emergent epileptiform activity in neural networks with weak excitatory synapses.
abstract: Brain electrical activity recorded during an epileptic seizure is frequently associated with rhythmic discharges in cortical networks. Current opinion in clinical neurophysiology is that strongly coupled networks and cellular bursting are prerequisites for the generation of epileptiform activity. Contrary to expectations, we found that weakly coupled cortical networks can create synchronized cellular activity and seizure-like bursting. Evaluation of a range of synaptic parameters in a detailed computational model revealed that seizure-like activity occurs when the excitatory synapses are weakened. Guided by this observation, we confirmed experimentally that, in mouse neocortical slices, a pharmacological reduction of excitatory synaptic transmission elicited sudden onset of repetitive network bursting. Our finding provides powerful evidence that onset of seizures can be associated with a reduction in synaptic transmission. These results open a new avenue to explore network synchrony and may ultimately lead to a rational approach to treatment of network pathology in epilepsy.
authors: Department of Pediatrics, Computation Institute of the University of Chicago, Chicago, IL 60637-1470, USA. wvandron@peds.bsd.uchicago.edu
authors: Wim
authors: W
authors: van Drongelen
authors: Hyong C
authors: HC
authors: Lee
authors: Mark
authors: M
authors: Hereld
authors: Zheyan
authors: Z
authors: Chen
authors: Frank P
authors: FP
authors: Elsen
authors: Rick L
authors: RL
authors: Stevens
mesh_terms: D000818:Animals; D001683:Biological Clocks; D003198:Computer Simulation; D004827:Epilepsy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D051379:Mice; D008959:Models, Neurological; D019579:Neocortex / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons; D009435:Synaptic Transmission