Ultrafast optical recording of spiking activity in a zebrafish neural circuit
Understanding how the brain’s many neurons coordinate their activity to perform behavioral tasks is a significant problem that, if solved, can lead to new developments in understanding and treating mental illness. Solving this problem requires careful examination of neural circuits in action. Current recording technologies are only partially up to this task, as they are unable to measure neural activity with sufficient spatial and temporal resolution. Existing electrical measurements are fast, but are insufficiently dense to measure many neurons within complex neural circuits. Similarly, existing optical measurements can perform parallel recordings on large scales, but cannot directly follow spiking activity. In order to better understand the details of coordinated neural activity, we need new tools that observe the spiking activity from many individual neurons simultaneously. My recent development of genetically encoded voltage sensors enables fluorescence microscopy to report both spiking and subthreshold voltage activity from individual neurons. Here, I propose to directly image the spikes from many neurons within the zebrafish brain, which serves as a model system similar to the human brain. We will use the unique capabilities of voltage imaging to analyze the spiking activity of a set of neurons that converts visual sensory information into motor output. In the long-term, my proposed research will serve as the gateway technology to access the spiking activity of all neurons in model animals, and to study how this population code drives behavior. In addition, voltage imaging in animal models is poised to study how genetic mutations lead to changes in spiking activity, which subsequently leads to neurological diseases; quantifying these currently unknown effects of genetic diseases will help uncover specific neural targets for clinical treatment.