FETCHO, J.R.; HIGASHIJIMA, S.; SUNY Stony Brook; SUNY Stony Brook: Optical and genetic studies of neuronal networks for movement I

Understanding the neuronal basis of behavior typically requires monitoring activity of the relevant neurons during behavior, working out the wiring diagrams of the circuits for the behavior of interest, and then perturbing the system to test the contribution of the neurons to behavior. Conventional approaches to studies of neuronal function depend upon recording from individual neurons with microeletrodes. These approaches provide essential information about activity patterns and connectivity, but are limited in their ability to easily monitor and perturb the activity of many neurons throughout the nervous system. We have been developing optical and genetic tools to study neuronal function that compliment electrophysiological methods. Our work focuses on the motor system of larval zebrafish and takes advantage of both the transparency of the fish as well as genetic tools available for zebrafish. By filling neurons with fluorescent calcium indicators, we can look into the intact fish and literally watch the active neurons light up when the fish performs a particular motor behavior. We have used this approach to explore which hindbrain and spinal neurons contribute to swimming and escape behaviors. By imaging several neurons at once, we have examined how activity in groups of spinal motoneurons and identified spinal interneurons varies with behavioral performance. In addition to monitoring activity, we can perturb activity by killing cells with a laser beam to assess more directly the behavioral contributions of neurons. Finally, genetics also allows for perturbation �experiments� through studies of mutant lines with extra neurons or mis-wired circuits. The combination of optical and genetic approaches with more conventional physiology allows for a powerful attack on the neuronal basis of behavior.