Special Chemical Biology Seminar

The brain encodes and processes information through the dynamic membrane voltage of neurons. However, tracking the change of membrane voltage of neurons at millisecond scale 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 excitable cells. Thus far, the performance of GEVIs has been a major bottleneck for in vivo measurements, which motivated me to undertake a directed evolution effort to engineer better GEVIs. In order to optimize the transient responses of biosensors, I developed a video-based platform to enable high-throughput pooled genetic screens in mammalian cells. I then used this system to develop far-red GEVIs with improved signal-to-noise ratios and kinetics. This screening platform can be applied to a variety of genotype-phenotype mapping questions where optical readouts are essential. Next, I will discuss how to combine these improved GEVIs with optogenetic perturbation to enable "all-optical electrophysiology" in the mouse brain. Using this approach, I quantified the strengths of chemical synapses and electrical synapses in the live mouse brain. Together, these molecular and optical tools will expand our ability to decipher the neural code.