title: Axotomized Corticospinal Neurons Increase Supra-Lesional Innervation and Remain Crucial for Skilled Reaching after Bilateral Pyramidotomy.
abstract: Skilled upper limb function heavily depends on the corticospinal tract. After bilateral lesions to this tract, motor control is disrupted but can be partially substituted by other motor systems to allow functional recovery. However, the remaining roles of motor cortex and especially of axotomized corticospinal neurons (CSNs) are not well understood. Using the single pellet retrieval task in adult rats, we induced significant recovery of skilled reaching after bilateral pyramidotomy by rehabilitative reaching training, and show that reach-related motor cortex activity, recorded in layer V, topographically reappeared shortly after axotomy. Using a chemogenetic neuronal silencing technique, we found that axotomized CSNs retained a crucial role for the recovered pellet retrieval success. The axotomized CSNs sprouted extensively in the red nucleus supplying new innervation to its magnocellular and parvocellular parts. Specific silencing of the rubrospinal tract (RST) also strongly abolished the recovered pellet retrieval success, suggesting a role of this cervically projecting nucleus in relaying cortical motor control. In summary, our results show that after bilateral corticospinal axotomy, motor cortex still actively engages in forelimb motor control and axotomized CSNs are crucially involved in the recovered reaching movement, potentially by relaying motor control via the RST.
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Mosberger
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Jenifer C
authors.initials: JC
authors.lastname: Miehlbradt
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bjelopoljak
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Schneider
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Anna-Sophia
authors.initials: AS
authors.lastname: Wahl
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Benjamin V
authors.initials: BV
authors.lastname: Ineichen
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gullo
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D019771:Axotomy / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D005552:Forelimb / Q000294:innervation / Q000502:physiology*; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans
keywords: electrophysiology; motor cortex; plasticity; reorganization; skilled reaching