DESCRIPTION (provided by applicant): Candidate: Dr. Robert Kotloski is a staff neurologist in the Epilepsy Center of Excellence and in the Traumatic Brain Injury/Polytrauma (TBI) clinics at the William S. Middleton Memorial Veterans Hospital. He is also a research fellow and instructor in the Department of Neurology at the University of Wisconsin. Dr. Kotloski has completed a combined MD/PhD degree at Duke University School of Medicine, during which time he studied molecular mechanisms of epileptogenesis. He has completed a residency in Neurology at Wake Forest University and a Clinical Neurophysiology fellowship with an epilepsy focus at the University of Wisconsin. He is applying for a VA CDA-2 award in order to obtain the career development training and support for scientific study to become an independent VA researcher. Environment: Dr. Kotloski will complete the proposed research at the VA and the University of Wisconsin. Both organizations provide an exceptionally collegial atmosphere and strong institutional support including protected time, research space, and equipment. The unique strains of in-bred rats are only available through the laboratory of a mentor, Dr. Thomas Sutula, and have not been used for TBI research previously. Career Plan: Dr. Kotloski's long-term career goals include the establishment of an independent, productive research laboratory focused on understanding TBI, post-traumatic epilepsy (PTE), and its comorbidities. Through his mentors, he will enhance his knowledge of animal models of epilepsy and TBI including cellular (Dr. Rutecki) and network (Dr. Sutula) mechanisms of epilepsy, and molecular mechanisms of TBI (Dr. Vemuganti). During the course of this proposal, he will hone his skills in manuscript and grant writing, mentoring, presentation, and laboratory management. Dr. Kotloski expects the proposed research and training will allow him to independently compete for VA Merit Review funding prior to the end of the CDA-2 award. Research Project: Current understanding of devastating residuals of TBI such as epilepsy is limited by a paucity of useful animal models. However a unique, plasticity-susceptible strain of rat, selected for increased rate of kindling, has demonstrated frequent post-traumatic seizures following moderate-to-severe TBI. The immediate goal of this proposal is to test the hypothesis that, following a traumatic brain injury, the development of epilepsy is preceded by changes in electrophysiologic activity and protein expression which are predictive of the later occurrence of PTE. Aim 1 is to characterize spontaneous electrographic changes and post-traumatic seizures after TBI in unique rat strains and out-bred rats. Two complementary strains of in-bred rats, one selected for increased rate of kindling (plasticity-susceptible) and another selected for decreased rate of kindling (plasticity-resistant), as well as out-bred Sprague-Dawley rats, will be studied. TBI will be induced by con...