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Spinal Circuits for the Control of Dextrous Movement

Award Number: U19NS112959
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Spinal Circuits for the Control of Dextrous Movement - Project Summary: Overall 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 for spinal circuit anatomical and functional dissection. To date, these genetic tools 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 the increased oversight of these behaviors 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 overall goal of this U19 Team-Research BRAIN Circuit Program proposal is two-fold: 1) the generation of a scalable, high-resolution atlas of forelimb-premotor interneurons in the cervical spinal cord that describes their connectivity, molecular phenotypes, electrophysiological properties, and functional contributions to forelimb behaviors, and 2) the development of testable predictive neural models that describe the network interactions that give rise to limb control. 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, the research plan 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, the Spinal Cord Circuit Team (TeamSCC) 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 sensorimotor circuits in the spinal cord to control movement.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/19/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $2,820,775 )
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/23/2023	NON-COMPETING CONTINUATION	$2,820,775
2023	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,820,775

Issue Date FY: 2022 ( Subtotal = $2,820,775 )
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	9/2/2022	NON-COMPETING CONTINUATION	$2,820,775
2022	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	9/1/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,820,775

Issue Date FY: 2021 ( Subtotal = $2,848,115 )
2021	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	9/9/2021	NON-COMPETING CONTINUATION	$2,848,115
2021	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,848,115

Issue Date FY: 2020 ( Subtotal = $2,840,384 )
2020	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/30/2020	NON-COMPETING CONTINUATION	$2,840,384
														Subtotal = $2,840,384

Issue Date FY: 2019 ( Subtotal = $2,981,129 )
2019	2019	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/6/2019	NEW	$2,981,129
														Subtotal = $2,981,129

Grand Total All Awards = $14,311,178

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Spinal Circuits for the Control of Dextrous Movement

Award Number: U19NS112959

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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