Evolving Fluorescent Indicators to Monitor Neuronal Voltage Dynamics in vivo

A longstanding goal in neuroscience is understanding how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision-making. Genetically Encoded Voltage Indicators (GEVIs) — light-emitting protein indicators whose brightness is modulated by voltage is a method for monitoring electrical dynamics. GEVIs are tools for monitoring voltage dynamics at high spatiotemporal resolution in genetically defined cell types. We use our novel high-throughput screening platform to develop novel indicators that are faster, brighter, and more sensitive and photostable. These new GEVIs enable the noninvasive recording of rapid voltage transients for extended durations and in deep cortical layers in awake behaving mice. We anticipate that our sensors will encourage neuroscientists —including those more familiar with calcium imaging— to exploit the unique advantages of voltage optical recording to decipher neuronal computations with millisecond-timescale resolution and cell type specificity.