jASAP voltage indicator optimization
ASAPs (Accelerated Sensor of Action Potentials), developed by Michael Lin (https://doi.org/10.1038/nn.3709, https://doi.org/10.1016/j.cell.2019.11.004), represents a class of voltage indicators that’s sensitive (from spike detection to subthreshold membrane potential reporting), fast (submillisecond level for recently published ASAP2f variant) and two-photon compatible. GENIE project team has put effort in optimizing ASAP voltage indicator. With our high-throughput HEK cell screening platform we identified one top hit, T392V mutation based on ASAP3, dramatically improve the sensitivity (by ~60%) without compromising kinetics. ASAP (T392V) variants performance was further tested in mammalian neurons (field stimulation screening and voltage clamp assay) and mouse visual cortex in vivo.