The past decade has seen dramatic improvements in genetically-encoded reporters of neural activity. However, capturing this activity at high speeds, over large volumes of the in intact brain and nervous system has remained a significant challenge. One technology that we have developed to address this problem is swept confocally aligned planar excitation (SCAPE) microscopy for high-speed 3D microscopy. SCAPE is a type of light sheet microscopy, but utilizes a novel scanning-descanning strategy to enable very high-speed volumetric cellular imaging with a versatile single, stationary objective at the sample. We are applying SCAPE to imaging awake, behaving organisms such as freely crawling Drosophila larvae, the whole brain of behaving adult Drosophila, zebrafish brain and the awake mouse cortex.

We have also developed wide-field optical mapping (WFOM) methods for imaging both neural activity and hemodynamics over the entire dorsal cortex in awake, behaving mice. This simple, yet powerful method enables longitudinal imaging of mice for a wide range of studies. We are using WFOM to study the mechanistic basis of neurovascular coupling, and the origins of signals detected in resting state fMRI in a range of conditions, including exploring the effects of drugs and disease on both behaviors and the neural and hemodynamic representations of those behaviors.

Both of these techniques are providing new high-speed, real time views of brain-wide activity in awake, behaving animals, providing fundamentally new observations of spontaneous activity and behavior. I will present our latest progress on high-speed imaging technique development, and showcase our work applying these techniques to understand whole-brain activity in the context of awake behavior and resting state networks.