title: Failure to form a stable topographic map during optic nerve regeneration: abnormal activity-dependent mechanisms.
abstract: 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.
authors.affiliation: School of Animal Biology, The University of Western Australia, Hackett Drive, Nedlands 6907, Western Australia, Australia. sarah@cyllene.uwa.edu.au
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Dunlop
authors.forename: R Victoria
authors.initials: RV
authors.lastname: Stirling
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodger
authors.forename: Andrew C E
authors.initials: AC
authors.lastname: Symonds
authors.forename: Wesley J
authors.initials: WJ
authors.lastname: Bancroft
authors.forename: Lisa B G
authors.initials: LB
authors.lastname: Tee
authors.forename: Lyn D
authors.initials: LD
authors.lastname: Beazley
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001931:Brain Mapping; D004594:Electrophysiology; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008116:Lizards; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000503:physiopathology; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014633:Valine; C409466:NR1 NMDA receptor; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; C104722:glutamate receptor ionotropic, AMPA 2