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Neural Plasticity and Myelin Dynamics after Amputation

Award Number: R01NS142032
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/05/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2030

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Neural Plasticity and Myelin Dynamics after Amputation - Project Summary/Abstract Traumatic accidents that cause unilateral denervation injuries are challenging experiences that requires motor learning and neural plasticity to overcome these types of injuries. Successful rehabilitation depends on learning to use a prosthesis or repaired nerve connections in addition to new skills with the intact limb. Despite advances in prosthesis and nerve repair technology, almost half of people abandon the use of prostheses, and most never regain complete function of repaired nerve connections. Others struggle to learn new motor skills with their intact limb. Learning these new skills depends on optimally functional and plastic neural connections, which are disrupted after unilateral denervation injury. Neural plasticity requires 1) circuit remodeling at the synaptic level and 2) support by glia, including oligodendrocyte-mediated wrapping of axons with myelin. High bilateral sensory cortex neural activity and white matter integrity loss are observed in people after unilateral injury. Both of these effects likely impair motor learning, but we lack an understanding of how these brain changes occur. Our lab has established a mouse whisker denervation model that mimics both the high neural activity and white matter loss observed in people after unilateral denervation injury. This model provides a unique opportunity to study the mechanisms the brain uses to adapt after unilateral denervation injury. The objective of this R01 application is to identify the mechanisms by which neural dysregulation and white matter integrity loss occur after unilateral denervation injury. We hypothesize that the chronically high neural activity that occurs after whisker denervation causes a loss in neuronal connectivity and a reduction in white matter integrity in the corpus callosum. We will test this hypothesis with the following Aims: 1) We will modulate specific groups of neurons to identify their role in causing dysregulated neural activity and white matter integrity loss. 2) We will use single nucleus RNA sequencing to identify signaling between neurons and oligodendrocytes to identify the molecular signaling between these groups of cells that cause these adaptations. 3) We will optimize in vivo training protocols to recruit the recruit mechanisms to prevent neural and white matter dysregulation after unilateral denervation injury. The techniques used in these Aims include intersectional viral labeling and modulation of specific neural connections, whole cell electrophysiology, histology, in vivo magnetic resonance imaging (MRI), single nucleus RNA sequencing, and clinically applicable behavioral intervention. Our long-term goal is to identify the mechanisms that the brain employs to adapt after injuries that disrupt signals arriving from the periphery. This proposal is significant because findings will support targeted therapies to improve motor learning and recovery after unilateral denervation injury. The proposed research is innovative because we study the interactions between neurons and oligodendrocyte lineage cells in a mouse model that mimics the phenotypes of people after unilateral denervation injury.


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 = $555,265 )
2026	2026	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/5/2026	NEW	$555,265
														Subtotal = $555,265

Grand Total All Awards = $555,265

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Neural Plasticity and Myelin Dynamics after Amputation

Award Number: R01NS142032

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/05/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2030

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