High-speed three-dimensional fluorescence imaging of neural activity

Our progress in understanding the function of the nervous system is, in many ways, limited by our ability to record neural activity. While there has been considerable progress in imaging at the extremes of length scales (e.g., whole brain imaging by fMRI and sub-cellular resolution by two-photon microscopy), there is a need for optical techniques to record the individual activities of large populations of neurons in intact circuits. Current techniques such as epifluorescence microscopy have reasonable time resolution but suffer from signal-to-background problems when viewing thick samples, while confocal techniques are limited in time resolution and/or photon efficiency. To address some of these limitations, we have developed a novel form of microscopy for high-speed three-dimensional fluorescence imaging. Using this technique, entire stacks of high signal-to-noise images can be acquired in seconds. We are currently using this technique to record the activity of populations of sensory neurons in the mouse olfactory system.