Neuronal and Circuitry Mechanisms of Epileptogenesis in a Complex in Vitro Model

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DESCRIPTION (provided by applicant): The goals of this sabbatical period include: 1) learn and apply a new, complex in vitro preparation to the study of circuitry in the CMS, including onset and spread of epilepsy; 2) apply imaging techniques to understand connectivity in this complex, in vitro preparation, including metabolic and intrinsic signal imaging (ie, NADH, IOS); 3) assess metabolic role of epilepsy, particularly the role of ketone bodies in suppressing epileptic onset and spread in zero magnesium model; 4) interact with the clinical assessment and surgical treatment of complex epilepsy syndromes. As a clinician-scientist I am interested in both the basic neuroscience of this complex in vitro model, since I can subsequently use this preparation in my funded research, as well as the interwoven basic and clinical neuroscience unit, in which Dr. Bernard is embedded. After assessing several possible USA sites for this sabbatical, this site in Marseille, France is unique in combining basic, translational and clinical neuroscience/neurosurgery into a tightly integrated unit, focused on a clinical entity, epilepsy, in which I am interested on several levels. As a senior fellow I intend to: (a) make a major change in research direction, focusing now more on epilepsy, a past but not currently funded interest; (b) broaden my scientific and clinical background, particularly because of the radically different approaches offered by this Inserm and the tightly interwoven research/clinical activities; (c) acquire new research capabilities, particular a new, complex in vitro preparation, further patch clamp recording experience, and imaging of this preparation; and (d) enlarge my command of the clinical epilepsy field, to which there is currently minimal exposure at Duke University. This award in particular will enable me to take time from my regular (extensive and very busy) professional responsibilities, as a neurosurgeon and clinician-scientist, to increase my capability in health-related epilepsy research. Since I have a wide variety of basic science, translational and clinical interests this Inserm unit is one of the few where all of these interests can be readily enhanced. For example, I am interested in recording and intracellular staining of interneurons and the role of these interneurons in developing and maintaining synchrony in the hippocampus, which is well suited to the complex in vitro preparation pioneered by Dr. Bernard. Also, the translational application of lab findings into the clinical epilepsy realm will be reviewed. The relevance of this research to new approaches to the study and analysis of epilepsy is very high, since this complex in vitro, preparation bridges simpler slice in vitro models with difficult in vivo models, by preserving complex circuitry relevant to the hippocampus.