Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks

Epilepsy is characterized by impaired circuit function and a propensity for spontaneous seizures, but how plastic rearrangements within the epileptic focus trigger cortical dysfunction and hyperexcitability is only partly understood. Here we have examined alterations in sensory processing and the underlying biochemical and neuroanatomical changes in tetanus neurotoxin (TeNT)-induced focal epilepsy in mouse visual cortex. We documented persistent epileptiform electrographic discharges and upregulation of GABAergic markers at the completion of TeNT effects. We also found a significant remodeling of the dendritic arbors of pyramidal neurons, with increased dendritic length and branching, and overall reduction in spine density but significant preservation of mushroom, mature spines. Functionally, spontaneous neuronal discharge was increased, visual responses were less reliable, and electrophysiological and behavioural visual acuity was consistently impaired in TeNT-injected mice. These data demonstrate robust, long-term remodeling of both inhibitory and excitatory circuitry associated with specific disturbances of network function in neocortical epilepsy.