In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long–Evans rats: relationship to spatial learning

Abstract

Using in vitro autoradiography, we investigated [ 3H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [ 3H]kainate and [ 3H] N-methyl- d-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24–25 months of age) Long–Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [ 3H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [ 3H]kainate binding in CA3 were reduced. In contrast, N-methyl- d-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [ 3H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl- d-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [ 3H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl- d-aspartate binding in the striatum and [ 3H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability. Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not neccessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial learning, suggesting a compensatory reduction in receptor binding in a subpopulation of aged rats.