Specializing in neurophysiological systems and cellular approaches to understanding neocortical function, developmental epilepsy and altered cognition due to traumatic brain injury
AREAS OF RESEARCH
Epilepsy and Developmental Malformations
Structural malformations of the cortex occurring during development are associated with epilepsy. Malformations commonly cause untreatable or intractable seizures. We employ optogenetics combined with neurophysiological recordings in a freeze lesion mouse model to understand the cellular and network mechanisms that contribute to this cortical hyperexcitability. We are currently pursuing possible treatments and preventions based on several decades of work in this model. Optogenetics = light sensitive ion channels genetically inserted into specific neuronal subtypes allowing control of neuronal activity levels through light application.
Mild Traumatic Brain Injury
There are more than 1.7 million traumatic brain injuries a year in the US alone. At least 75% of them are mild. To mimic mild injury without contusion, we use the fluid percussion injury model. This creates diffuse axonal injury (DAI) wherein neocortical neurons with a severed axon lie adjacent to neurons with intact axons. We have shown that both the axotomized and the intact population within the injured brain are physiologically different from those in naïve or sham-injured brain. Pyramidal neurons show altered intrinsic and synaptic properties. Our new grant focuses on abnormalities in inhibitory interneurons and changes at the axon initial segment of pyramidal neurons.
Currently most models of post-traumatic epilepsy involve a severe injury despite the fact that there are thousands more patients that develop epilepsy after only a mild traumatic brain injury. Our goal is to develop a model of epilepsy using video EEG-identified seizures that occurs after mild traumatic brain injury.