Repeated seizures lead to altered skilled behaviour and are associated with more highly efficacious excitatory synapses

Abstract

People with epilepsy have a high incidence of interictal behavioural problems that appear to be related to the location of their seizure focus. This study investigated a novel test of the hypotheses that repeated seizures result in behavioural deficits and altered performance during the interictal state, and that those behaviours are related to the presence of more highly efficacious excitatory synapses. We tested these hypotheses by first repeatedly eliciting seizures with electric current through indwelling electrodes in the corpus callosum at the level of the caudal forelimb area of sensorimotor neocortex in the rat. We then assessed learned skilled behaviours that primarily utilize the forelimbs on tasks that are sensitive to the functional integrity of that structure. We observed both behavioural deficits and altered kinematic performance in rats that experienced repeated neocortical seizures relative to an electrode-implanted control group. From a separate set of rats, tissue was prepared for quantification of thickness and excitatory synaptic subtypes from neocortical layer V. We observed significantly increased numbers of perforated synapses that make their connections directly onto the dendritic shaft at 3 weeks following the last seizure. Altered reaching behaviours are likely due to neural reorganization in the neocortex including more efficacious synapses.