The brain encodes and processes information through the dynamic membrane voltage of neurons. However, in vivo electrophysiology, i.e., the study of the membrane voltage of individual cells in live animals, has been a major challenge for neuroscience. In this seminar, I will present voltage imaging, an emerging technology using genetically encoded voltage indicators (GEVIs) to visualize the membrane voltage dynamics of cells. Voltage imaging can be combined with optogenetic stimulation to enable “all-optical electrophysiology”, a technology that enabled cell membrane voltage to be simultaneously recorded and perturbed with light, opening a path for high-throughput electrophysiology study in live animals. Thus far, the performance of GEVIs has been a bottleneck for many applications. I will describe my directed evolution effort to improve a far-red GEVI. In order to optimize the transient voltage response of this biosensor, I developed a novel video-based pooled screening platform that enabled thousands of genetic variants to be screened expeditiously. Using this platform, I developed far-red GEVIs with improved signal-to-noise ratios and kinetics. Importantly, this platform may be adapted for many types of genetic screens where optical readouts are required. I will discuss the application of these new GEVIs for tracking electric signal propagation within neurons. In particular, I will demonstrate how to use voltage imaging and all-optical electrophysiology to understand neuron network dynamics in the live mouse brain. Together, these molecular and optical tools will greatly expand our ability to decipher the brain.
Talk will be in-person and virtual, see information below.