Consequences of axon guidance defects on the development of retinotopic receptive fields in the mouse colliculus

J Physiol. 2009 Mar 1;587(Pt 5):953-63. doi: 10.1113/jphysiol.2008.160952. Epub 2009 Jan 19.

Abstract

Gradients of molecular factors pattern the developing retina and superior colliculus (SC) and guide retinal ganglion cell (RGC) axons to their appropriate central target perinatally. During and subsequent to this period, spontaneous waves of action potentials sweep across the retina, providing an instructive topographic signal based on the correlations of firing patterns of neighbouring RGCs. How these activity-independent and activity-dependent factors interact during retinotopic map formation remains unclear. A typical phenotype of mutant mice lacking genes for one or more RGC axon guidance molecules is the presence of topographically inappropriate projections or 'ectopic spots'. Here, we examine mice that lack functional bone morphogenetic protein receptors (BMPRs) in the retina. Retinal BMP controls the graded expression of RGC axon guidance molecules, resulting in some dorsal RGCs projecting ectopically to locations in the SC that normally receive input from ventral retina. We examine the consequences of this anatomical phenotype in vivo by studying the receptive field (RF) properties of neurons in the superficial SC. We observe a mixture of physiological phenotypes in BMPR mutant mice; notably we find some neurons with ectopic RFs displaced in elevation, corresponding to the observed anatomical defect. However, in a result not necessarily congruent with the presence of focal ectopic projections, some neurons have split, enlarged and patchy/distorted RFs. These results are consistent with the effects of spontaneous retinal waves acting upon a disrupted molecular template, and they place significant limits on the form of an activity-dependent learning rule for the development of retinocollicular projections.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / physiology*
  • Bone Morphogenetic Protein Receptors / deficiency
  • Bone Morphogenetic Protein Receptors / genetics
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Photic Stimulation / methods
  • Retina / growth & development*
  • Retinal Ganglion Cells / physiology
  • Superior Colliculi / growth & development*
  • Visual Fields / genetics
  • Visual Fields / physiology*
  • Visual Pathways / growth & development*

Substances

  • Bone Morphogenetic Protein Receptors