RP2: Connectivity and Circuit Organization

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Project Summary: Project 2 – Connectivity and Circuit Organization Neural circuits in the cervical spinal cord generate a range of rhythmic and dexterous motor behaviors that are essential for life. These circuits, aside from being important in their own right, serve as a window into how other brain areas are functionally organized by providing a critical readout of behavior, namely motor action. The analyses in this project will use cutting-edge genetic tools and anatomical approaches, many of which were developed at the Salk Institute, to create a scalable and interactive connectivity map of the pre- motor interneuron circuits in the cervical spinal cord. This connectivity map will be registered to motor pools innervating specific forelimb muscles in order for the connectivity datasets to be informative for the modeling and interpretation of motor behaviors that are key components of this Team SCC initiative. Intersectional mouse genetics will be used to target specific populations of spinal interneurons and annotate key information about position, and connectivity, in order to generate a physical wiring diagram for forelimb pre- motor circuits. The pre-motor wiring diagram will serve as a template for a subsequent more expansive analysis of spinal connectivity that will include sensory, propriospinal, and descending connections to forelimb pre-motor neurons. These studies, when completed, will provide unparalleled insights into the organization of the spinal motor circuitry and the motor system as a whole. They will also lead to a better understanding of the cellular interactions and neural computations that give rise to rhythmic and skilled forelimb movements.