Epilepsy following head trauma often appears after a quiescent period of months or years. In the rat """"""""undercut"""""""" model of posttraumatic epileptogenesis, tetrodotoxin (TTX) treatment will prevent epileptogenesis, allowing comparison of epileptogenic and nonepileptogenic injured neocortex. More information about changes in cortical circuitry and changes in receptor fimction following epileptogenic injuries is fundamental to progress in developing prophylaxis or new treatments suitable for humans. This project focuses on the function and critical role of ionotropic glutamatergic receptor-mediated excitation in the undercut model. Patch clamp techniques will be used to evaluate miniature, spontaneous and evoked excitatory currents and unitary responses of synaptically coupled pairs of pyramidal neurons in epileptogenic and nonepileptogenic injured neocortical slices from rats several weeks following surgical cortical isolations. Each of these indices will be quantified to provide complementary information about the state of functional excitation in chronically epileptogenic cortex. The project will be carried out in the fully equipped and well supported epilepsy research laboratory of the Department of Neurology and Neurological Sciences at Stanford University. The sponsor has trained numerous students and fellows, many of whom are now prominent in the field of neurophysiology and epilepsy. An outstanding neuroscience faculty, a critical mass of postdoctoral fellows in the Stanford Epilepsy Training Program, numerous seminars and courses are available to enrich and supplement the laboratory training. This fellowship is an important step in the acquisition of technical acumen and research experience that will be crucial in developing a successful academic career as a clinician/scientist and independent investigator in epilepsy.
| Graber, Kevin D; Prince, David A (2004) A critical period for prevention of posttraumatic neocortical hyperexcitability in rats. Ann Neurol 55:860-70 |
