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The assembly and function of sensory-motor circuits in the developing spinal cord


A fundamental question in the study of motor control is how the nervous system accomplishes the complex task of integrating commands from multiple movement systems in order to perform a motor behavior. Even the simplest tasks, such as withdrawing the limb from a painful stimulus or taking a single step, involve multiple areas of the brain and spinal cord. Examples of movement parameters that are encoded within the nervous system include the selection and timing of muscle contraction in order to move a body region to a desired position, and the coordination of multiple body joints and body regions. Significant progress has been made in the field to understand the contribution of individual cell types to motor control, as well as the genetic mechanisms that regulate the development of individual cell types. However, the circuit components that link multiple motor control populations, as well as the mechanisms that regulate the formation of integrative motor networks, are poorly understood.

This dissertation describes a series of original work that aims to elucidate the cellular players and developmental mechanisms that assemble circuit components into functional neural networks. The first chapter provides a framework for understanding how different motor control pathways are organized within the central nervous system. The second chapter describes a group of premotor neurons that are located in the deep dorsal horn of the spinal cord, receive input from multiple motor control pathways, and bind together the activity of multiple motor pools. Importantly, genetic markers (Satb1, Satb2, and tcfAP2β) were identified that, to date, comprise the most significant fraction of molecularly defined premotor neurons in the spinal cord.

The third chapter describes a novel population of cells that express the genetic marker Satb2, spinal interneurons that are located at the intersection of incoming sensory and outgoing motor information. This work examines the role of the Satb2 gene in spinal interneuron development, as well as sensory-motor circuit assembly and function. This work provides an important contribution to our understanding of the organizational logic of integrative spinal networks and the types of movements they control.

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