Competition with primary sensory afferents drives remodeling of corticospinal axons in mature spinal motor circuits

Abstract

Injury to the mature motor system drives significant spontaneous axonal sprouting instead of axon regeneration. Knowing the circuitlevel determinants of axonal sprouting is important for repairing motor circuits after injury to achieve functional rehabilitation. Competitive interactions are known to shape corticospinal tract axon outgrowth and withdrawal during development. Whether and how competition contributes to reorganization of mature spinal motor circuits is unclear. To study this question, we examined plastic changes in corticospinal axons in response to two complementary proprioceptive afferent manipulations: (1) enhancing proprioceptive afferents activity by electrical stimulation; or (2) diminishing their input by dorsal rootlet rhizotomy. Experiments were conducted in adult rats. Electrical stimulation produced proprioceptive afferent sprouting that was accompanied by significant corticospinal axon withdrawal and a decrease in corticospinal connections on cholinergic interneurons in the medial intermediate zone and C boutons on motoneurons. In contrast, dorsal rootlet rhizotomy led to a significant increase in corticospinal connections, including those on cholinergic interneurons; C bouton density increased correspondingly. Motor cortex-evoked muscle potentials showed parallel changes to those of corticospinal axons, suggesting that reciprocal corticospinal axon changes are functional. Using the two complementary models, we showed that competitive interactions between proprioceptive and corticospinal axons are an important determinant in the organization of mature corticospinal axons and spinal motor circuits. The activity- and synaptic space-dependent properties of the competition enables prediction of the remodeling of spared corticospinal connection and spinal motor circuits after injury and informs the target-specific control of corticospinal connections to promote functional recovery.

Publication DOI: https://doi.org/10.1523/JNEUROSCI.3441-15.2016
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Funding Information: This work was supported by National Institutes of Health Grant 2R01NS064004 (J.H.M.), Craig H. Neilsen Foundation Grant 261214 (J.H.M.), and New York State Department of Health Spinal Cord Injury Research Board Grant C030172 (J.H.M.). We thank Hiroki Kimu
Additional Information: Copyright © 2016 the authors. Articles are released under a Creative Commons Attribution License after a 6 months embargo
Uncontrolled Keywords: Activity dependent plasticity,Corticospinal tract,Motor cortex,Proprioceptive afferents,Rat,Neuroscience(all)
Publication ISSN: 1529-2401
Last Modified: 20 May 2024 16:22
Date Deposited: 28 Oct 2019 13:24
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.jne ... ontent/36/1/193 (Publisher URL)
PURE Output Type: Article
Published Date: 2016-01-06
Accepted Date: 2015-11-18
Authors: Jiang, Yu Qiu
Zaaimi, Boubker (ORCID Profile 0000-0003-0210-8747)
Martin, John H.

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