This is a collaboration between experts at UCSD, UCLA, UCSF, UC Davis, UCI and the Ecole Polytechnique Federale de Lausanne (EPFL) to examine plasticity and regeneration in the non-human primate spinal cord. Our goal is to enhance knowledge and translational relevance of research on spinal cord injury (SCI). This project will map the motor cortex ?connectome? to better understand the primate motor network in both the intact state and after recovery from SCI, and will focus on promoting therapeutic growth of the most important motor control system in primates, the corticospinal projection.
Aim 1 : The Intact Primate Corticospinal Connectome Aim 1 will map the intact connectome for motor control of the hand using new generation, highly specific and highly sensitive viral tools. These findings will be correlated with motor cortex recordings and forelimb EMG activity in awake, behaving subjects. These tools will allow an unprecedented understanding of hand motor control in the primate, thereby revealing novel mechanisms of motor control and identifying new targets for therapy.
Aim 2 : The Lesioned Primate Corticospinal Connectome How does injury affect the corticospinal connectome? How does the corticospinal system adapt to injury and alter its set of outputs, and how does this influence functional recovery? We will use the elegant and novel tools of Aim 1 to map the injured, reorganized corticospinal connectome, motor cortex dynamics, and forelimb EMG after C7 hemisection lesions.
Aim 3 : Spinalized Neural Stem Cell Grafts to Enhance Corticospinal Repair Work in Aim 3 will build on recent progress in neural stem cell technology. We will use ?spinalized? neural stem cells to augment growth of the injured corticospinal tract and form trans- lesion relays that enhance recovery of forelimb function after SCI. Further, we will compare the connectome of the corticospinal system after therapeutic stimulation to its intact and lesioned state. This work will reveal how new corticospinal growth after injury impacts the projections and connections of this vitally important motor system in humans. 1

Public Health Relevance

This research program aims to provide an unprecedented understanding of the brain network that controls hand function, and to stimulate regeneration of this system after injury, in an animal model that could most closely predict human benefit. This is a collaborative endeavor between six research groups working closely together to accelerate understanding and discovery of therapies for human nervous system injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZRG1-BDCN-Q (02)M)
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Jakeman, Lyn B
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Rosenzweig, Ephron S; Brock, John H; Lu, Paul et al. (2018) Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat Med 24:484-490
Dulin, Jennifer N; Adler, Andrew F; Kumamaru, Hiromi et al. (2018) Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts. Nat Commun 9:84
Kumamaru, Hiromi; Lu, Paul; Rosenzweig, Ephron S et al. (2018) Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into Neural Progenitor Cell Grafts. Stem Cell Reports 11:861-868
Patel, Akash; Li, Zhongzhi; Canete, Philip et al. (2018) AxonTracer: a novel ImageJ plugin for automated quantification of axon regeneration in spinal cord tissue. BMC Neurosci 19:8
Salegio, Ernesto A; Bresnahan, Jacqueline C; Sparrey, Carolyn J et al. (2016) A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta). J Neurotrauma 33:439-59
Nielson, Jessica L; Haefeli, Jenny; Salegio, Ernesto A et al. (2015) Leveraging biomedical informatics for assessing plasticity and repair in primate spinal cord injury. Brain Res 1619:124-38