DESCRIPTION (provided by applicant): Vital to the study and treatment of important neuropathies, such as epilepsy and stroke is an understanding of the neuronal network processes responsible for higher brain functions. Complex, highly interconnected functions such as memory, decision making, and motor control depend on intracortical parallel processing, which may be investigated, ideally, with a minimally invasive technology having both high temporal and spatial resolution. The objective of this proposal is to develop a minimally-invasive method of imaging neural activity in isolated nerves and in small animal brain slices. Specifically, this method targets near-real-time, single-axon resolution imagining of the important parallel processing that occurs in complex neuronal networks. The method images nearly-instantaneous manifestations of neural activation, and should ultimately be able to provide moving-picture images of action potential propagation. We will demonstrate that the method is capable of imaging, in reflectance mode and with single- axon resolution, the local optical birefringence changes that accompany electrical activity in complex neuronal networks by imaging the changes in optical polarization elipticity. We will first develop a system capable of imaging the stimulated activity in individual nerves (i.e. crayfish and/or lobster) and then progress to measurements in hypocampus brain slices from a rat model. Testing will include imaging the effects of seizure induction and drug response. Results of this project will lay the groundwork for two important future advances: 3-D imaging of neural activation patterns in brain slices by integration of the birefringence imaging into sectioning microscopy and, ultimately, real-time imaging of activation patterns in the exposed cortex of small animals, in vivo. The objective of this proposal is to develop a minimally-invasive method of imaging neural activity in isolated nerves and in small animal brain slices, with high temporal and spatial resolution. Such a tool will aid in the study and treatment of important neuropathies, such as epilepsy and stroke, and can help provide an understanding of the neuronal network processes responsible for higher brain functions.