Development and Evolution of Tetrapod Motor Circuits

Introduction

A hallmark of the nervous system is its rich cell-type diversity, its intricate connectivity, and its coordinated patterns of activity. Behavior largely is an emergent property of this complexity. Thus, to understand behavior, we must define neurons’ molecular, cellular, and functional properties.

Challenge of Motor Circuits

This task has proven especially challenging for motor circuits with their readily apparent output in motor activity but astonishingly heterogeneous populations of neurons. To parse this complexity, I propose a novel approach harnessing the unique behavioral switch during Xenopus frog metamorphosis.

Metamorphic Transition

The metamorphic 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. Here, I aim to define the molecular, functional, and behavioral features of swim-to-limb circuit complexification during frog metamorphosis— a crucial step in developing this new model (Aim 1: OBSERVE).

Developmental Mechanisms

Next, I will identify the developmental mechanisms that drive the profound change in circuit composition and output. I will evaluate the contribution of increasing cellular heterogeneity to pre- and post-metamorphic neuron activity and behavior (Aim 2: PERTURB).

Cross-Species Comparison

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: COMPARE). Such intra- and inter-species approaches will deepen our understanding of the origin of tetrapod motor complexity and its relationship to motor circuit composition and output.

Significance of the Study

My work will be the first comprehensive study of the genetics, activity, and behavior of a swim-to-limb transition in a single organism. It will draw bridges between studies of motor control from different species and generate hypotheses and knowledge for understanding motor circuit development, function, and dysfunction all the way to a clinical setting.