Congenital absence of corticospinal tract does not severely affect plastic changes of the developing postnatal spinal cord

Neuroscience. 2015 Aug 20:301:338-50. doi: 10.1016/j.neuroscience.2015.06.017. Epub 2015 Jun 14.

Abstract

The arrival and refinement of corticospinal afferents are likely to influence the maturation of the spinal cord and sensory-motor networks. To understand this better, we studied the revision of monosynaptic muscle afferents, the expression of activity-related genes, neurotrophins and their receptors in the cervical spinal cord from postnatal day (P) 0 to 21. We compared control and Celsr3|Emx1 mice, in which corticospinal axons never develop. The corticospinal tract (CST), labeled by anti-protein kinase C gamma (PKCγ) antibody in the dorsal funiculus, increased gradually in the control, but was never visible in the mutant. Using anti-parvalbumin and choline acetyltransferase double immunostaining, close contacts between proprioceptive afferent fibers and spinal motor neurons appeared at P0 and were gradually eliminated thereafter, with no difference between control and mutant mice. In both genotypes, the number of parvalbumin-positive interneurons increased similarly from P7 to P21, and a comparable upregulation of c-Jun protein was seen at P7. Contrary to control samples, in which ciliary neurotrophic factor (CNTF) protein levels increased from P0 to P7 and gradually decreased after P14, CNTF concentrations were time-invariant in mutant samples. The dynamic profile of neurotrophin-3 (NT3) expression was also moderately affected in mutant mice. In control spinal cord, NT3 was increased at P7 and decreased at P14, but remained more stable in mutant samples. In contrast, expression profiles of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase (Trk) B, TrkC, p75 neurotrophin receptor (p75(NTR)) and glial cell-line-derived neurotrophic factor (GDNF) were similar in both genotypes. In conclusion, with the possible exception of CNTF and NT3 expression, most events that accompany maturation of the spinal cord appear largely independent of corticospinal inputs.

Keywords: Celsr3; axonal elimination; c-Jun; corticospinal tract; neural activity; neurotrophins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Cadherins / genetics
  • Gene Expression Regulation, Developmental / genetics*
  • Homeodomain Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Nerve Tissue Proteins / metabolism
  • Pyramidal Tracts / abnormalities*
  • Receptors, Cell Surface / genetics
  • Spinal Cord Diseases / genetics*
  • Spinal Cord Diseases / pathology*
  • Spinal Cord* / abnormalities
  • Spinal Cord* / growth & development
  • Spinal Cord* / pathology
  • Transcription Factors / genetics

Substances

  • Cadherins
  • Celsr3 protein, mouse
  • Homeodomain Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Transcription Factors
  • empty spiracles homeobox proteins