A hallmark of the nervous system is its rich cell-type diversity and intricate patterns of connectivity and activity. Behavior largely is an emergent property of this complexity. Thus, to understand behavior, we must define neuron’s molecular, cellular and functional properties. This task has proven especially challenging for motor circuits: with readily apparent output patterns of motor activity; yet, astonishingly heterogeneous populations of neurons. To parse this complexity, I propose a novel approach harnessing the unique behavioral switch during Xenopus frog metamorphosis. This transition from simple swimming to more complex, coordinated limb movement offers an ideal opportunity to study the expansion and diversification of two motor circuits in one organism. I aim to identify and compare fundamental principles of motor circuit organization and function. First, I will define the molecular, functional and behavioral features of swim-to-limb circuit complexification (Aim 1)—a crucial step in developing this new model of motor circuit diversity. Next, I will identify the developmental mechanisms that drive this profound change in circuit composition and output, and evaluate the contribution of increasing cellular heterogeneity to pre- and post-metamorphic neuron activity and behavior (Aim 2). Finally, to define the conserved and divergent circuit features for swimming and walking across evolution, I will expand to a cross-species approach comparing frogs/mice and fish/tadpoles (Aim 3). These intra- and inter- species comparisons will deepen our understanding of the drivers of tetrapod motor complexity and its relationship to motor circuit composition and output. My findings will carry beyond motor circuits, defining generalizable mechanisms of development and function of nervous system heterogeneity that may even become applicable in clinical settings.
