Expression of vesicular glutamate transporter 1 in the mouse retina reveals temporal ordering in development of rod vs. cone and ON vs. OFF circuits

J Comp Neurol. 2003 Oct 27;465(4):480-98. doi: 10.1002/cne.10838.


Glutamatergic transmission is crucial to the segregation of ON and OFF pathways in the developing retina. The temporal sequence of maturation of vesicular glutamatergic transmission in rod and cone photoreceptor and ON and OFF bipolar cell terminals is currently unknown. Vesicular glutamate transporters (VGLUTs) that load glutamate into synaptic vesicles are necessary for vesicular glutamatergic transmission. To understand better the formation and maturation of glutamatergic transmission in the rod vs. cone and ON vs. OFF pathways of the retina, we examined the developmental expression of VGLUT1 and VGLUT2 immunocytochemically in the mouse retina. Photoreceptor and bipolar cell terminals showed only VGLUT1-immunoreactivity (-IR); no VGLUT2-IR was present in any synapses of the developing or adult retina. VGLUT1-IR was first detected in cone photoreceptor terminals at postnatal day 2 (P2), several days before initiation of ribbon synapse formation at P4-P5. Rod terminals showed VGLUT1-IR by P8, when they invade the outer plexiform layer (OPL) and initiate synaptogenesis. Developing OFF bipolar cell terminals showed VGLUT1-IR around P8, 2-3 days after bipolar terminals were first identified in the inner plexiform layer (IPL) by labeling for the photoreceptor and bipolar cell terminal marker, synaptic vesicle protein 2B. Although terminals of ON bipolar cells were present in the IPL by P6-P8, most did not show VGLUT1-IR until P8-P10 and increased dramatically from P12. These data suggest a hierarchical development of glutamatergic transmission in which cone circuits form prior to rod circuits in both the OPL and IPL, and OFF circuits form prior to ON circuits in the IPL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • Carrier Proteins / metabolism*
  • Cell Differentiation / physiology*
  • Glutamic Acid / metabolism
  • Immunohistochemistry
  • Interneurons / cytology
  • Interneurons / metabolism
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / cytology
  • Neural Pathways / growth & development*
  • Neural Pathways / metabolism
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Retina / cytology
  • Retina / growth & development*
  • Retina / metabolism
  • Retinal Cone Photoreceptor Cells / cytology
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / cytology
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / metabolism
  • Synaptic Vesicles / ultrastructure
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • Membrane Transport Proteins
  • Slc17a7 protein, mouse
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Transport Proteins
  • Glutamic Acid