Population imaging of neural activity in awake behaving mice

A longstanding goal in neuroscience has been to image membrane voltage across a population of individual neurons in an awake, behaving mammal. Here, we report a genetically encoded fluorescent voltage indicator, SomArchon, which exhibits millisecond response times and compatibility with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable, by several-fold over previously published reagents(1-8). Under conventional one-photon microscopy, SomArchon enables population analysis of approximately a dozen neurons at once, in multiple brain regions: cortex, hippocampus, and striatum, of head-fixed, awake, behaving mice. Using SomArchon, we detected both positive and negative responses of striatal neurons during movement, previously reported by electrophysiology but not easily detected using modern calcium imaging techniques(9-11), highlighting the power of voltage imaging to reveal bidirectional modulation. We also examined how spikes relate to subthreshold theta oscillations of individual hippocampal neurons, with SomArchon reporting that individual neurons’ spikes are more phase locked to their own subthreshold theta oscillations than to local field potential theta oscillations. Thus, SomArchon reports both spikes as well as subthreshold voltage dynamics in awake, behaving mice.