title: Selective alterations in glutamate receptor subtypes after unilateral orbital enucleation.
abstract: Glutamate is the major excitatory neurotransmitter in the rat visual system. Using quantitative autoradiography the effect of unilateral orbital enucleation on [3H]kainate, [3H]alpha-amino-3-hydroxy-5-methyl- isoxazole-4-propionic acid [( 3H]AMPA) and [3H]glutamate binding to kainate, quisqualate and NMDA receptors respectively has been examined within anatomical components of the visual pathway at 4 time points up to 20 days post-lesion. The time course for the degeneration of retinal projection fibres was assessed in a separate group of animals by quantifying [3H]cyclohexyladenosine [( 3H]CHA) binding to presynaptic adenosine A1 receptors. Over the first 5 days after orbital enucleation, there were no significant alterations in glutamate or adenosine A1 receptor binding in visual structures of the visually deprived hemisphere. However, at 10 days post-lesion [3H]AMPA binding was significantly reduced (30%) in the visually deprived superior colliculus but unaltered in other visual structures. At this time point there was also a significant reduction (50%) in [3H]CHA binding in the visually deprived superior colliculus but not in other retino-recipient nuclei. There were similar changes in [3H]AMPA and [3H]CHA binding at 20 days post-enucleation. [3H]Kainate binding was significantly increased in the visually deprived superior colliculus only at 20 days post-enucleation. Saturation analysis of [3H]kainate and [3H]AMPA binding at this time point indicated a selective increase in the Bmax value for the high affinity [3H]kainate binding site and a concomitant decrease in the Bmax value for the high affinity [3H]AMPA binding site in the visually deprived superior colliculus. There were, however, no significant alterations in [3H]AMPA or [3H]kainate binding in other primary projection areas or in secondary visual areas (e.g. visual cortex) at any time point. NMDA sensitive [3H]glutamate binding was unaltered in the visually deprived hemisphere up to 20 days post-enucleation. These results suggest an upregulation of kainate receptors in the visually deprived superior colliculus after orbital enucleation and a loss of presynaptic quisqualate receptors on degenerating retinal fibres. The plastic alterations in kainate receptors in the superior colliculus are supportive of electrophysiological data suggesting a physiological role for these sites in mediating excitatory postsynaptic potentials in tectal neurons.
authors.affiliation: Wellcome Surgical Institute, Glasgow, U.K.
authors.forename: D T
authors.initials: DT
authors.lastname: Chalmers
authors.forename: J
authors.initials: J
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D015353:Eye Enucleation; D007839:Functional Laterality; D005971:Glutamates / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D009799:Ocular Physiological Phenomena; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D014316:Tritium; D014793:Visual Cortex / Q000378:metabolism*; D014795:Visual Pathways / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D005971:Glutamates; D007051:Ibotenic Acid; D007608:Kainic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid