Emergence of Functional Network Dynamics from Single Cell Properties

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Project Summary/Abstract The collective dynamics of the network of neurons in the brain drive its primary holistic function — control of organismal behavior. Pathologies of the nervous system that disrupt this coordinated activity result in dysfunctional patterns of motor output and gross behavior. However, it is unknown how patterns of coordinated activity arise from the properties of single neurons and their connections. In the next five years we seek to develop a rigorous theory and biologically realistic model of the emergence of coordinated dynamics in a complete network of neurons, similar to the current level of understanding of how the dynamics of interacting molecular species produce goal-directed motile behavior in single-cell bacteria. We focus on the relatively simple nervous system of C. elegans; with precisely 302 neurons, it is a natural choice for such fundamental neurodynamical studies. To attack this problem, the research in our lab utilizes a fusion of experimental and computational approaches including advanced microscopy, genomic engineering, machine learning based image processing, quantitative behavior, and dynamical systems analysis. We have developed novel approaches to quantitatively probe and characterize the signal processing properties of single neurons as well as record and quantify the activity of the entire C. elegans nervous system at single-cell resolution using volumetric calcium imaging under genetic perturbation. We are now exploring the relationship between the microscopic properties of cellular signaling and the macroscopic function of collective network dynamics. A mechanistic model of the composition and maintenance of structured, controlled brain dynamics would provide a framework for understanding how gross neurological disease states arise from cellular and molecular dysfunction.