In Vivo Optical Mapping of Rodent Neocortical Epilepsy

Weill Medical College Of Cornell Univ, New York NY

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Abstract

Epilepsy is a disease affecting 1-2% of the population. Electrical recordings from chronic animal models and human neocortical epileptic foci indicate that the population of neurons underlying each interictal epileptiform discharge varies over time. The spatial relationship between interictal events and the ictal onset zone, thought to be the critical area of epileptogenesis, is not well understood and critical to the surgical treatment of epilepsy. Electrophysiological recording methods, although currently the "gold standard", are inadequate to address these questions based on restrictions due to volume conduction or sampling limitations, many of which can be overcome with optical recording techniques. The PI is a fellowship trained epilepsy surgeon at UMDNJ with extensive laboratory experience in optical recording of neuronal activity, both in vitro and in vivo. In a second post-doctoral fellowship, the PI demonstrated that in vivo optical recording of intrinsic signals can be used to generate high-resolution, real-time maps of the population of neurons participating in an epileptiform event. The goal of the current study is to examine the shifting spatio-temporal dynamics of the epileptogenic aggregate in both acute and chronic experimental models of in vivo rodent epilepsy. In the laboratory of mentor Gyorgy Buzsaki, a world-renowned expert in electrophysiological mapping of rodent epilepsy at Rutgers and part of the joint UMDNJ-Rutgers Graduate Center m Newark-Program in Neurosciences, we will first determine the precise relationship between the optical signal and the interictal and ictal epileptiform events using well-established acute and chronic in vivo rodent models. Optical epilepsy maps will be correlated with maps derived from electrophysiological recordings from a grid of surface electrodes, multicontact silicon probes, as well as c fos hybridization. Additional technical support in optical recording and data analysis will be provided by collaborator Ralph Siegel, also a member of the UMDNJ- Rutgers Graduate Center in Newark-Program in Neurosciences. As a related goal, optically-guided surgical resections of epileptogenic cortex will ascertain the required volume of epileptogenic tissue which must be removed to eliminate seizures. The results of these investigations will not only be important in understanding the pathophysiology of neocortical epilepsy but also critical in optimizing surgical treatment of human clinical epilepsy. Following the period of mentorship, the PI will be able to combine independent basic science research in a separate laboratory at UMDNJ with clinical optical recordings in the operating room during the neurosurgical treatment of epilepsy.