Development of the visual pathway is disrupted in mice with a targeted disruption of the calcium channel beta(3)-subunit gene

J Comp Neurol. 2001 Nov 12;440(2):177-91. doi: 10.1002/cne.1378.


Refinement of the retinal pathways to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is mediated by nitric oxide (NO). Long-term depression (LTD) can also be induced in SC and LGN during the time at which these pathways are refined, and this LTD is partially dependent on NO and L-type Ca(2+) channel function. In an effort to determine whether NO-mediated pathway refinement is also mediated by Ca(2+) channel function, we have examined the refinement of the retinocollicular and retinogeniculate pathways in mice which lack the gene for the Ca(2+) channel beta(3) subunit (CCKO) and which have significantly reduced L-type Ca(2+) currents. Injections of the anterograde tracer cholera toxin subunit B/HRP were made into one eye of these knockout animals and in wild-type mice ages postnatal day (P) 13, P19, and P26. After 48 hours, mice were perfused and sections processed by using tetramethylbenzidine histochemistry. Labeling distribution in some animals was analyzed quantitatively. Obvious differences in the distribution of the ipsilateral retinocollicular pathway were observed at P15, with the pathway being more exuberant in CCKO mice. This difference was statistically significant. More subtle differences were seen at P21 and P28. Obvious differences were also seen in the contralateral retinogeniculate pathway which in CCKO mice filled most of the domain normally occupied by ipsilateral eye fibers. This difference was also statistically significant. We conclude that reduction in L-type Ca(2+) currents has an effect on axonal refinement similar to that which occurs in NO knockout mice, which supports the possibility that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Axons / metabolism
  • Axons / ultrastructure
  • Body Patterning / genetics
  • Brain / cytology
  • Brain / growth & development*
  • Brain / metabolism
  • Calcium Channels, L-Type / deficiency*
  • Calcium Channels, L-Type / genetics
  • Cell Differentiation / genetics
  • Cholera Toxin
  • Down-Regulation / genetics
  • Female
  • Functional Laterality / physiology
  • Geniculate Bodies / cytology
  • Geniculate Bodies / growth & development
  • Geniculate Bodies / metabolism
  • Male
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / anatomy & histology
  • Mice, Knockout / growth & development*
  • Mice, Knockout / metabolism
  • Neural Inhibition / genetics*
  • Neuronal Plasticity / genetics*
  • Nitric Oxide / metabolism*
  • Retina / cytology
  • Retina / growth & development
  • Retina / metabolism
  • Signal Transduction / genetics
  • Superior Colliculi / cytology
  • Superior Colliculi / growth & development
  • Superior Colliculi / metabolism
  • Visual Pathways / cytology
  • Visual Pathways / growth & development*
  • Visual Pathways / metabolism


  • Calcium Channels, L-Type
  • Nitric Oxide
  • Cholera Toxin