Michael Lin (Stanford)

Speaker: Michael Lin (Stanford)
Title: Mapping electricity in the nervous system: the quest for 1 millisecond and 1 millivolt
Host: Ikuko Smith
Lab website: https://linlab.stanford.edu/

Abstract: Understanding how neuronal circuits encode, process, and transmit information is a central goal of neuroscience. A long-standing challenge has been to record transmembrane voltage across space and in real time, as voltage is the native currency of neural computation and its kinetics set the limits of processing speed. Fluorescent genetically encoded voltage indicators (GEVIs) have thus long been desired, but the dual requirements for sensing action potentials of brief durations and subthreshold potentials of low amplitude have presented a severe Early fluorescent voltage indicators were constrained by speed or sensitivity, but recent generations of genetically encoded voltage indicators (GEVIs) now achieve single-trial detection of both subthreshold events and action potentials in vivo. In this talk, I will describe advances from our ASAP family of GEVIs, which enable high-speed, high-contrast voltage imaging with both one- and two-photon microscopy. ASAP5 extends voltage imaging into the domain of dendritic physiology, revealing synaptic potentials distributed along dendritic trees with millisecond resolution. ASAP6 further broadens voltage recording throughput, enabling widefield imaging of hundreds of neurons in densely labeled circuits. Direct comparison of ASAP6 with the fast calcium indicator GCaMP8f highlights their complementary strengths, including opposite dependencies of signal-to-noise ratio on frame rate and distinct temporal regimes in which each modality has advantages. Finally, I will discuss emerging opportunities for non-invasive imaging of neuronal activity using neurotransmitter bioluminescent reporters engineered from marine luciferases.