Large-scale cellular-resolution voltage imaging of the zebrafish brain

Duke University, Durham NC

Investigators

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Abstract

Abstract Recording the spiking activity of many individual neurons in a densely packed region of the brain has been a standing challenge for the neuroscience community. Recently developed in genetically encoded voltage indicators have sufficiently fast kinetics to record action potentials with millisecond temporal resolution from single neurons the brains of live model organisms. These sensors offer hope of large scale recordings of neuron spikes. The next advance toward understanding the brain as network system will parallelize the existing single cell recordings over many neurons in disparate regions of the brain. To achieve such increased scales and field-of- view, I propose to create and validate the next generation of fast optical voltage recording techniques that scale over large areas and depths of the zebrafish brain. This proposal focuses on three aims that will enhance neural recordings: (1) I will construct a hybrid light-sheet light-field microscope that will image multiple depths of the zebrafish brain simultaneously with cellular resolution, 500 Hz temporal resolution, and reduce computational costs. (2) I will construct an oblique illumination light-sheet microscope with a newly developed CMOS camera that is capable of sampling individual layers within the zebrafish brain at micrometer resolution and 10 kHz frame rate, resulting in a high spatial resolution, ultra-fast volumetric view of the zebrafish brain. (3) I will create a new class of genetically encoded voltage indicators with superior brightness and reduced background noise. The combination of the three aims will establish the methods to explore spiking activity simultaneously over the entire zebrafish brain. These methods will generalize to address a variety of neuroscience questions pertaining to interaction between different neural systems; my optical schemes will better interpret neural activity by recording the large-scale correlation between neurons in different systems.