SEARCH

SEARCH BY CITATION

Keywords:

  • cerebral palsy;
  • cJun;
  • immunocytochemistry;
  • motor cortex;
  • muscimol;
  • parvalbumin

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.