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Dissecting spinal interneuron circuits to augment neurological recovery in Degenerative Cervical Myelopathy (DCM)

Award Number: R01NS134644
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Dissecting spinal interneuron circuits to augment neurological recovery in Degenerative Cervical Myelopathy (DCM) - Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury (SCI), characterized by pain, sensory deficits, fine motor dysfunction, and impaired gait and balance. Individuals with DCM report upper limb functional deficits as particularly disabling due to decreased independence and quality of life. Although surgical spinal cord decompression is the primary treatment of DCM and leads to functional improvements for most patients, over 30%, do not achieve meaningful clinical recovery of motor function, and over 40% report substantial residual impairment. Currently, no subsequent strategies are available to improve neurological recovery following surgical intervention; as such, patients may continue to live with a disability. Changes in neural circuits governing forelimb function in DCM are unknown. This knowledge gap impedes the development of treatments to improve upper limb function after decompression surgery. Targeted neuromodulation of spinal interneurons (INs) is a potential therapeutic strategy for DCM that is expected to enhance forelimb function. V2a and dI3, genetically-defined spinal interneuron populations, have been shown to play critical roles in integrating supraspinal, proprioceptive, and cutaneous sensory inputs in forelimb reaching and grasping tasks. Further, recent data demonstrate that spinal dI3 INs are crucial during neonatal development of motor circuits and following SCI. As such, we hypothesize that following surgical decompression, activation of dI3 INs is necessary for the recovery of forelimb function, and stimulation of these INs will enhance forelimb recovery. Aim 1 will determine the changes in descending cortical and peripheral sensory input onto cervical dI3 INs associated with forelimb deficits in a mouse model of DCM. In Aim 2, we determine if dI3 INs underpin plasticity in forelimb function that occurs after DCM and after surgical decompression. Finally, Aim 3 will examine the efficacy of stimulating cervical dI3 INs in enhancing forepaw motor recovery following decompressive surgery. The current proposal will be the first to determine how the neuronal integration of dI3 INs is altered in DCM such that dI3 INs become a necessary component of the grasping function in DCM. The successful completion of this project will guide future research by (1) determining the plasticity of dI3 INs within the forelimb neural network in DCM, (2) uncovering the sensorimotor mechanism associated with dI3 neuronal plasticity in DCM, and (3) demonstrating the efficacy of targeted neuromodulation as a promising treatment strategy for DCM. We expect our results to facilitate the development of neuromodulation treatments to augment recovery of upper limb function after surgery for DCM.


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: 2025 ( Subtotal = -$147,375 )
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	007	2	5/12/2025	SUPPLEMENT FOR EXPANSION	-$1
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	2	5/12/2025	NON-COMPETING CONTINUATION	-$1
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	4/17/2025	SUPPLEMENT FOR EXPANSION	-$55,464
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	11/26/2024	SUPPLEMENT FOR EXPANSION	$55,465
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/22/2024	NON-COMPETING CONTINUATION	$253,023
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	4/17/2025	NON-COMPETING CONTINUATION	-$253,022
2025	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	1	5/12/2025	SUPPLEMENT FOR EXPANSION	-$12,216
2025	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	1	5/12/2025	NEW	-$135,159
														Subtotal = -$147,375

Issue Date FY: 2024 ( Subtotal = $278,813 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/1/2024	NEW	$255,702
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	1	7/11/2024	SUPPLEMENT FOR EXPANSION	$23,111
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	7/11/2024	NEW	$0
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	3/6/2024	NEW	$0
														Subtotal = $278,813

Grand Total All Awards = $131,438

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Dissecting spinal interneuron circuits to augment neurological recovery in Degenerative Cervical Myelopathy (DCM)

Award Number: R01NS134644

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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