IRFP: Scanless Two-Photon Voltage Imaging of Live Neuron Activity With Holographic Wavefront Shaping

Foust Amanda J, Hamden CT

Investigators

Abstract

The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twenty-four month research fellowship by Dr. Amanda J. Foust to work with Dr. Valentina Emiliani at Université Paris Descartes, Paris, France. Voltage imaging has the potential to revolutionize our understanding of how neuronal cells and circuits process and store information through a mixture of analog and digital electrical signaling in the living brain. However, low signal-to-noise ratios and high background have prevented spatial and temporal resolution adequate for tracking electrical activity on cellular and subcellular length scales in-vivo. Light sculpturing techniques such as Gradient Phase Contrast (GPC) and temporal focusing (TF) under development in Dr. Valentina Emiliani's laboratory can improve the spatial resolution of voltage imaging techniques by enabling targeted fluorescence excitation of specified cells and substructures. To this end, we are developing, adapting, and optimizing wavefront shaping technology for imaging the propagation of electrical activity in the axons and dendrites of neurons with voltage-sensitive dyes and fluorescent proteins. Development of wavefront shaping technology for spatially targeted voltage sensing will provide a powerful tool for investigating the electrical underpinnings of sensation, perception, cognition, and behavior. Moreover, these techniques can be used to determine what fundamental circuit alterations occur with neurological diseases and disorders such as epilepsy and multiple sclerosis, and inform development of more effective therapeutic strategies.