Grant: Operating Grant

Epilepsy is the most common and expensive neurological disorder worldwide. Between seizures people with epilepsy may have any number of behavioural comorbidities that include anxiety/depression, memory disruption, sexual dysfunction, sensory and motor disturbances. My laboratory has documented motor disturbances in rats that had seizures elicited from the area in the neocortex that regulates forelimb movement. Furthermore, neocortical movement representations or "motor maps" become larger in rats with seizures much like the anomalous motor maps reported in people with frontal lobe epilepsy. Thus, we have developed a homologous rat model for the altered motor behaviour and motor map reorganization observed in a population of people with frontal lobe epilepsy. The framework for this grant application is that alterations in neural network functioning underlies inter-ictal behavioural comorbidities with epilepsy. Neural network functioning can be assessed by deriving high resolution motor maps. The motor maps are in turn based on the interplay between excitatory and inhibitory cells and seizures alter the synaptic communication and/or cellular firing properties of the cells in the neocortical circuits. Through the studies proposed here we will test the general hypothesis that expansion and reorganization of neural networks, manifested as changes in motor maps, will be related to alterations in motor behaviours in rats. This grant utilizes a multi-level integrated approach that encompasses the behavioural, network, cellular and synaptic levels. The novelty and innovative aspects of these studies are based upon the fact that my laboratory is the only one that uses detailed kinematic behavioural analysis and high resolution intracortical microstimulation to derive motor maps following induced seizures. Thus my laboratory is in a unique position to discover the relationship between functional network level organization and skilled motor behaviour after seizures.