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Natural and targeted circuit reorganization after spinal cord injury

Abstract

A spinal cord injury disrupts communication between the brain and the circuits in the spinal cord that regulate neurological functions. The consequences are permanent paralysis, loss of sensation and debilitating dysautonomia. However, the majority of circuits located above and below the injury remain anatomically intact, and these circuits can reorganize naturally to improve function. In addition, various neuromodulation therapies have tapped into these processes to further augment recovery. Emerging research is illuminating the requirements to reconstitute damaged circuits. Here, we summarize these natural and targeted reorganizations of circuits after a spinal cord injury. We also advocate for new concepts of reorganizing circuits informed by multi-omic single-cell atlases of recovery from injury. These atlases will uncover the molecular logic that governs the selection of 'recovery-organizing' neuronal subpopulations, and are poised to herald a new era in spinal cord medicine.

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Fig. 1: Adaptive and maladaptive reorganization of brain, brainstem and spinal circuits following spinal cord injury.
Fig. 2: Neuromodulation of anatomically intact circuits.
Fig. 3: Mechanisms through which epidural electrical stimulation restores hemodynamics and mobility.
Fig. 4: Biological strategies to reconstitute damaged circuits.

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Acknowledgements

We acknowledge support from Defitech Foundation, the Swiss National Science Foundation (Ambizione Fellowship PZ00P3_185728 to M.A.A.) and subsidy to G.C. (310030_192558), Swiss National Science Foundation (32003BE_205563), European Research Council (ERC-2015-CoG HOW2WALKAGAIN 682999; Marie Sklodowska-Curie individual fellowship 842578 to J.W.S.), H2020-MSCA-COFUND-2016 EPFL Fellows program (665667 to C.K.), the Morton Cure Paralysis Foundation (to M.A.A.), the ALARME Foundation (to M.A.A. and G.C.) and the Human Frontiers in Science Program long-term fellowship (LT001278/2017-L to C.K.).

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Correspondence to Grégoire Courtine.

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G.C., J.B. and J.W.S. hold various patents in relation with some of the present work. G.C. and J.B. are consultants of ONWARD medical. G.C. and J.B. are minority shareholders of ONWARD, a company with partial relationships with some of the presented work. The remaining authors declare no competing interests.

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Anderson, M.A., Squair, J.W., Gautier, M. et al. Natural and targeted circuit reorganization after spinal cord injury. Nat Neurosci 25, 1584–1596 (2022). https://doi.org/10.1038/s41593-022-01196-1

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