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Published September 2021 | Accepted Version
Journal Article Open

Formation of a novel supraspinal-spinal connectome that relearns the same motor task after complete paralysis

Abstract

Having observed that electrical spinal cord stimulation and training enabled four patients with paraplegia with motor complete paralysis to regain voluntary leg movement, the underlying mechanisms involved in forming the newly established supraspinal-spinal functional connectivity have become of great interest. van den Brand et al. (Science 336: 1182–1185, 2012) subsequently, demonstrated the recovery, in response to spinal electro-neuromodulation and locomotor training, of voluntary stepping of the lower limbs in rats that received a lesion that is assumed to eliminate all long-descending cortical axons that project to lumbosacral segments. Here, we used a similar spinal lesion in rats to eliminate long-descending axons to determine whether a novel, trained motor behavior triggered by a unique auditory cue learned before a spinal lesion, could recover after the lesion. Hindlimb stepping recovered 1 mo after the spinal injury, but only after 2 mo, the novel and unique audio-triggered behavior was recovered, meaning that not only was a novel connectivity formed but also further evidence suggested that this highly unique behavioral response was independent of the recovery of the circuitry that generated stepping. The unique features of the newly formed supraspinal-spinal connections that mediated the recovery of the trained behavior is consistent with a guidance mechanism(s) that are highly use dependent.

Additional Information

© 2021 the American Physiological Society. Received 7 July 2020; Accepted 30 July 2021; Published online 18 August 2021; Published in print 1 September 2021. We thank the technical help provided by S. Zdunowski. This research was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institute of Neurological Disorders and Stroke (NINDS) 1U01EB015521 and U01EB007615; and the Dana & Albert R. Broccoli Charitable Foundation and Nanette, Burt Forester, including matching by PwC LLP; and Roberta Wilson and Christopher and Dana Reeve Foundation. Disclosures: V.R.E. holds shareholder interest in NeuroRecovery Technologies and holds certain inventorship rights on intellectual property licensed by the Regents of the University of California to NeuroRecovery Technologies. V.R.E. holds shareholder interest in spineX Inc. and holds certain inventorship rights on intellectual property licensed by the Regents of the University of California to spineX Inc. V.R.E. serves on the scientific advisory board of in vivo Therapeutics and ArianRF and serves as the Chair of the Scientific Advisory board at spineX. None of the other authors has any conflicts of interest, financial or otherwise, to disclose. Author Contributions: L.S.U., J.W.B., and V.R.E. conceived and designed research; L.S.U., M.A.T., K.L.I.D., E.A.D., and H.Z. performed experiments; L.S.U. analyzed data; L.S.U., M.A.T., K.L.I.D., P.E.P., and J.W.B. interpreted results of experiments; L.S.U. prepared figures; L.S.U. and V.R.E. drafted manuscript; L.S.U., P.E.P., J.W.B., and V.R.E. edited and revised manuscript; L.S.U., M.A.T., K.L.I.D., E.A.D., H.Z., P.E.P., J.W.B., and V.R.E. approved final version of manuscript.

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Additional details

Created:
August 22, 2023
Modified:
October 23, 2023