title: Motor Cortex Activity Organizes the Developing Rubrospinal System.
abstract: The corticospinal and rubrospinal systems function in skilled movement control. A key question is how do these systems develop the capacity to coordinate their motor functions and, in turn, if the red nucleus/rubrospinal tract (RN/RST) compensates for developmental corticospinal injury? We used the cat to investigate whether the developing rubrospinal system is shaped by activity-dependent interactions with the developing corticospinal system. We unilaterally inactivated M1 by muscimol microinfusion between postnatal weeks 5 and 7 to examine activity-dependent interactions and whether the RN/RST compensates for corticospinal tract (CST) developmental motor impairments and CST misprojections after M1 inactivation. We examined the RN motor map and RST cervical projections at 7 weeks of age, while the corticospinal system was inactivated, and at 14 weeks, after activity returned. During M1 inactivation, the RN on the same side showed normal RST projections and reduced motor thresholds, suggestive of precocious development. By contrast, the RN on the untreated/active M1 side showed sparse RST projections and an immature motor map. After M1 activity returned later in adolescent cat development, RN on the active M1/CST side continued to show a substantial loss of spinal terminations and an impaired motor map. RN/RST on the inactivated side regressed to a smaller map and fewer axons. Our findings suggest that the developing rubrospinal system is under activity-dependent regulation by the corticospinal system for establishing mature RST connections and RN motor map. The lack of RS compensation on the non-inactivated side can be explained by development of ipsilateral misprojections from the active M1 that outcompete the RST. Significance statement: Skilled movements reflect the activity of multiple descending motor systems and their interactions with spinal motor circuits. Currently, there is little insight into whether motor systems interact during development to coordinate their emerging functions and, if so, the mechanisms underlying this process. This study examined activity-dependent interactions between the developing corticospinal and rubrospinal systems, two key systems for skilled limb movements. We show that the developing rubrospinal system competes with the corticospinal system in establishing the red nucleus motor map and rubrospinal tract connections. This is the first demonstration of one motor system steering development, and ultimately function, of another. Knowledge of activity-dependent competition between these two systems helps predict the response of the rubrospinal system following corticospinal system developmental injury.
authors.affiliation: Department of Physiology, Pharmacology, and Neuroscience, City College of the City University of New York, New York, New York 10031.
authors.forename: Preston T J A
authors.initials: PT
authors.lastname: Williams
authors.affiliation: Department of Physiology, Pharmacology, and Neuroscience, City College of the City University of New York, New York, New York 10031 jmartin@ccny.cuny.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Martin
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D002415:Cats; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D009044:Motor Cortex / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D012012:Red Nucleus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*
chemical_list: D018755:GABA Agonists; D009118:Muscimol
keywords: corticospinal tract; development; motor cortex; red nucleus; rubrospinal tract; spinal cord