Failure to form a stable topographic map during optic nerve regeneration: abnormal activity-dependent mechanisms

Exp Neurol. 2003 Dec;184(2):805-15. doi: 10.1016/j.expneurol.2003.08.013.


Visually evoked responses in the optic tectum are mediated by glutamate receptors. During development, there is a switch from N-methyl-d-aspartate (NMDA)- to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated activity as the retinotectal map refines and visual function ensues. A similar pattern is seen in goldfish as the map refines during optic nerve regeneration. Here we examined glutamate receptors during optic nerve regeneration in the lizard, Ctenophorus ornatus, in which an imprecise retinotopic map forms transiently but degrades, leaving animals blind via the experimental eye. Receptor function was examined using NMDA and AMPA/kainate antagonists during in vitro tectal recording of visually evoked post-synaptic extracellular responses. Expression of NR1 (NMDA) and GluR2 (AMPA) receptor subtypes was examined immunohistochemically. In unoperated control animals, responses were robust and AMPA/kainate receptor-mediated. When the imprecise map was present, responses were difficult to evoke and insecure; periods of spontaneous activity as well as inactivity were also noted. Although AMPA/kainate-mediated activity persisted and GluR2 immunoreactivity increased transiently, NMDA receptor-mediated activity was also consistently detected and NR1 expression increased. In the long term, when the map had degraded, responses were readily evoked and predominantly AMPA/kainate receptor-mediated although some NMDA-mediated activity and NR1 expression remained. We suggest that the asynchronous activity reaching the optic tectum results in an inability to recapitulate the appropriate functional sequences of expression of NMDA and AMPA/kainate receptors necessary to refine the retinotectal map.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain Mapping*
  • Electrophysiology
  • Evoked Potentials, Visual / drug effects
  • Evoked Potentials, Visual / physiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Immunohistochemistry
  • Lizards
  • Nerve Crush
  • Nerve Regeneration / physiology*
  • Optic Nerve / physiology*
  • Optic Nerve Injuries / physiopathology
  • Quinoxalines / pharmacology
  • Receptors, AMPA / biosynthesis
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism*
  • Receptors, Kainic Acid / drug effects
  • Receptors, Kainic Acid / metabolism
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Time Factors
  • Valine / analogs & derivatives*
  • Valine / pharmacology


  • Excitatory Amino Acid Antagonists
  • NR1 NMDA receptor
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • FG 9041
  • 2-amino-5-phosphopentanoic acid
  • Valine
  • glutamate receptor ionotropic, AMPA 2