DESCRIPTION There is a great interest in imaging neuronal activity based on changes in fast intrinsic optical signals (e.g. changes in light scattering and phase) that occur on a millisecond timescale. Fast intrinsic optical signals are related to alteration in the complex refractive index and small volume changes near the neuron membrane, in response to the rapid osmotic changes associated with ion fluxes during action potentials. Optical coherence tomography (OCT) is an emerging biomedical imaging technology that provides label-free and depth-resolved images with micron-scale spatial resolution and sub-millisecond temporal resolution. OCT relies on detection of intrinsic optical contrast, eliminating the need for potentially toxic exogenous contrast agents or genetically- encoded indicators. OCT achieves over 100 dB sensitivity, enabling it to detect weak scattering changes associated with neuronal activity. In addition, OCT has extremely good phase sensitivity (

PUBLIC HEALTH RELEVANCE: We plan to develop and validate a label-free and ultrafast optical imaging technology to record millisecond timescale activities associated with action potentials with single neuron resolution. This technology can be used to investigate behavior of thousands of neurons in a network simultaneously, with the potential to significantly impact fundamental brain research.