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SCC Martyn D Goulding Spinal Circuits for the Control of Dexterous Movement
Title: Spinal Circuits for the Control of Dexterous Movement
Abstract: Local networks within the spinal cord represent an essential computational layer for the control of limb-driven motor behaviors, integrating descending and sensory inputs to coordinate dexterous motor output. Significant advances have been made in characterizing the developmental programs that specify the core cardinal interneuron types that make up these motor networks. This knowledge has been used to develop a battery of mouse genetic reagents, which have been primarily used to study locomotion and spinal reflexes in the lumbar spinal cord.
Given the wider range of dexterous motor behaviors that are produced by cervical circuits and their modulation by descending motor pathways, the mouse cervical spinal cord provides a unique and tractable mammalian model system for understanding how coordinated movements are generated by local motor networks and how these motor behaviors are regulated by the brain. The functional interrogation and modeling of these circuits, based on real behavioral outcomes and detailed information about the cell types that generate these behaviors, will ensure that the overall project is greater than the sum of its parts. Specifically, we will address two overarching questions: 1) How do rhythmic spinal networks control non-rhythmic movements, which represent the majority of forelimb motor behaviors, and 2) How are these spinal circuits modified to control more complex joint movements to achieve forelimb dexterity? To address these questions, we will generate: (a) a pre-motor interneuron connectome that includes information on cell positions and synaptic weightings, (b) a comprehensive index of the physiological properties and molecular identities of genetically distinct neuronal subtypes within each cardinal interneuron class, (c) a functional description of spinal circuit control of natural forelimb motor behaviors, and (d) a working model of the motor network that describes how circuit connectivity and dynamics give rise to key elements of forelimb behavior. Ultimately, these data will be used to generate a searchable web-based portal with 3D visualization tools linked to the molecular, electrophysiological, functional, and network model databases. Together, this work will lead to a deeper understanding of the organization and function of cervical circuitry, which will be of great value to groups that are grappling with the issue of how motor centers in the brain communicate with spinal sensorimotor circuits to control movement.
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