title: Spinal cord plasticity in response to unilateral inhibition of the rat motor cortex during development: changes to gene expression, muscle afferents and the ipsilateral corticospinal projection.
abstract: In developing Wistar albino rats, ventral horn muscle afferent boutons are lost following corticospinal innervation. Motor cortex lesions rescue a proportion of these boutons and perturb activity dependent expression of cJun and parvalbumin (PV) in the spinal cord. Therefore, we tested whether activity-dependent competition between corticospinal and proprioreceptive afferents determines the balance of these inputs to motor output pathways by delivering the inhibitory GABA agonist muscimol unilaterally to the forelimb motor cortex using slow release polymer implants from postnatal day 7 (P7) coincident with corticospinal synaptogenesis. Controls received saline. Inhibition of immature cortical neurons by muscimol was confirmed with separate in vitro electrophysiological recordings. After P28, spinal cord sections were immunostained for PV, cJun and muscle afferents transganglionically labelled with cholera toxin-B (CTB). Unilateral inhibition reduced contralaterally the number of PV positive spinal cord neurons and muscle afferent boutons in the dorsolateral ventral horn, compared to controls, and significantly altered the distribution of motoneuronal cJun expression. Separately, descending tracts were retrogradely traced with CTB from the cervical hemicord contralateral to implants. Forelimb sensorimotor cortex sections were immunostained for either CTB or PV. In muscimol treated animals, significantly fewer neurons expressed PV in the inhibited hemicortex, but as many CTB labelled corticospinal neurons were present as in controls, along with an equally large corticospinal projection from contralateral to the implant, significantly greater than in controls. Unexpectedly, unilateral inhibition of the motor cortical input did not lead to an expanded muscle afferent input. Instead, this was reduced coincident with development of a bilateral corticospinal innervation.
authors.affiliation: Neural Development, Plasticity and Repair Group, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom. g.j.clowry@ncl.ac.uk
authors.forename: G J
authors.initials: GJ
authors.lastname: Clowry
authors.forename: B M
authors.initials: BM
authors.lastname: Davies
authors.forename: N S
authors.initials: NS
authors.lastname: Upile
authors.forename: C L
authors.initials: CL
authors.lastname: Gibson
authors.forename: P M
authors.initials: PM
authors.lastname: Bradley
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D002772:Cholera Toxin / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004525:Efferent Pathways / Q000254:growth & development / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D007839:Functional Laterality / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D009044:Motor Cortex / Q000166:cytology / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D011145:Polyvinyls; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D018755:GABA Agonists; D010320:Parvalbumins; D011145:Polyvinyls; D016755:Proto-Oncogene Proteins c-jun; C016438:ethylenevinylacetate copolymer; D009118:Muscimol; D002772:Cholera Toxin; D002795:Choline O-Acetyltransferase