Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice

Qi Han, Josue D. Ordaz, Nai-Kui Liu, Zoe Richardson, Wei Wu, Yongzhi Xia, Wenrui Qu, Ying Wang, Heqiao Dai, Yi Ping Zhang, Christopher B. Shields, George M. Smith and Xiao-Ming Xu ()
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Qi Han: Indiana University School of Medicine
Josue D. Ordaz: Indiana University School of Medicine
Nai-Kui Liu: Indiana University School of Medicine
Zoe Richardson: Indiana University School of Medicine
Wei Wu: Indiana University School of Medicine
Yongzhi Xia: Indiana University School of Medicine
Wenrui Qu: Indiana University School of Medicine
Ying Wang: Indiana University School of Medicine
Heqiao Dai: Indiana University School of Medicine
Yi Ping Zhang: Norton Healthcare
Christopher B. Shields: Norton Healthcare
George M. Smith: Temple University
Xiao-Ming Xu: Indiana University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.

Date: 2019
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DOI: 10.1038/s41467-019-13854-3

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