PT - JOURNAL ARTICLE AU - Kiryl D. Piatkevich AU - Seth Bensussen AU - Hua-an Tseng AU - Sanaya N. Shroff AU - Violeta Gisselle Lopez-Huerta AU - Demian Park AU - Erica E. Jung AU - Or A. Shemesh AU - Christoph Straub AU - Howard J. Gritton AU - Michael F. Romano AU - Emma Costa AU - Bernardo L. Sabatini AU - Zhanyan Fu AU - Edward S. Boyden AU - Xue Han TI - Population imaging of neural activity in awake behaving mice in multiple brain regions AID - 10.1101/616094 DP - 2019 Jan 01 TA - bioRxiv PG - 616094 4099 - http://biorxiv.org/content/early/2019/04/23/616094.short 4100 - http://biorxiv.org/content/early/2019/04/23/616094.full AB - A longstanding goal in neuroscience has been to image membrane voltage, with high temporal precision and sensitivity, in awake behaving mammals. Here, we report a genetically encoded 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 manyfold over previous reagents. SomArchon only requires conventional one-photon microscopy to achieve these high performance characteristics. These improvements enable population analysis of neural activity, both at the subthreshold and spiking levels, in multiple brain regions – cortex, hippocampus, and striatum – of awake behaving mice. Using SomArchon, we detect both positive and negative responses of striatal neurons during movement, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examine how the intracellular subthreshold theta oscillations of hippocampal neurons govern spike output, finding that nearby cells can exhibit highly correlated subthreshold activities, even as they generate highly divergent spiking patterns.