PT - JOURNAL ARTICLE AU - Shay Ohayon AU - Antonio M. Caravaca-Aguirre AU - Rafael Piestun AU - James J. DiCarlo TI - Deep brain fluorescence imaging with minimally invasive ultra-thin optical fibers AID - 10.1101/116350 DP - 2017 Jan 01 TA - bioRxiv PG - 116350 4099 - http://biorxiv.org/content/early/2017/03/13/116350.short 4100 - http://biorxiv.org/content/early/2017/03/13/116350.full AB - A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well-defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive (surface) multiphoton approaches1,2 for deep (>2mm) structures, while Gradient Refreactive Index (GRIN) endoscopes2–4 are thick and cause significant damage upon insertion. Here, we demonstrate a novel microendoscope to image neural activity at arbitrary depths via an ultrathin multimode optical fiber (MMF) probe that is 5-10X thinner than commercially available microendoscopes. We demonstrate micron-scale resolution, multispectral and volumetric imaging. In contrast to previous approaches1,5–8 we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator. Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.