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]α-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 A 1 receptors. Over the first 5 days after orbital enucleation, there were no significant alterations in glutamate or adenosine A 1 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 b max value for the high affinity [ 3H]kainate binding site and a concomitant decrease in the b max 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.