Project Summary: To understand the function of neural circuits in the brain and spinal cord, one would like to perturb specific neurons and to measure the response of the targeted and neighboring cells. Optical methods provide approaches for both actuating and sensing. Light-sensitive ion channels have been engineered to actuate neurons. The Cohen Lab and others developed a protein-based voltage indicator with enhanced brightness and sensitivity to changes in voltage. One can co-express the actuator and the sensor in the same cells to achieve all-optical electrophysiology with single-spike time resolution, good sensitivity to subthreshold voltage dynamics, and the possibility to probe many neurons at once.

The project aims to express the actuating and sensing constructs in zebrafish larvae. Zebrafish are transparent, which greatly simplifies optical actuation and sensing. Establishing a system to perform optical electrophysiology in zebrafish opens many interesting research possibilities. We propose to study functional connectivity by observing how activation or inhibition of a certain neuron influences its neighbors. We will focus on the zebrafish central pattern generator (CPG) in the spinal cord which is involved in the regulation of locomotion. We hope to learn how different neuronal activation patterns regulate transitions between different swimming speeds.