Pathway-specific genetic attenuation of glutamate release alters select features of competition-based visual circuit refinement

Neuron. 2011 Jul 28;71(2):235-42. doi: 10.1016/j.neuron.2011.05.045.


A hallmark of mammalian neural circuit development is the refinement of initially imprecise connections by competitive activity-dependent processes. In the developing visual system retinal ganglion cell (RGC) axons from the two eyes undergo activity-dependent competition for territory in the dorsal lateral geniculate nucleus (dLGN). The direct contributions of synaptic transmission to this process, however, remain unclear. We used a genetic approach to reduce glutamate release selectively from ipsilateral-projecting RGCs and found that their release-deficient axons failed to exclude competing axons from the ipsilateral eye territory in the dLGN. Nevertheless, the release-deficient axons consolidated and maintained their normal amount of dLGN territory, even in the face of fully active competing axons. These results show that during visual circuit refinement glutamatergic transmission plays a direct role in excluding competing axons from inappropriate target regions, but they argue that consolidation and maintenance of axonal territory are largely insensitive to alterations in synaptic activity levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Animals, Newborn
  • Biophysics / methods
  • Cells, Cultured
  • Cholera Toxin / metabolism
  • Electric Stimulation / methods
  • Functional Laterality
  • Geniculate Bodies / physiology
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Mice
  • Mice, Mutant Strains
  • Retina / cytology*
  • Retinal Ganglion Cells / physiology*
  • Statistics, Nonparametric
  • Synaptic Transmission / genetics
  • Vesicular Glutamate Transport Protein 2 / deficiency
  • Vesicular Glutamate Transport Protein 2 / genetics
  • Visual Pathways / anatomy & histology
  • Visual Pathways / growth & development*


  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • Green Fluorescent Proteins
  • Glutamic Acid
  • Cholera Toxin