Changes in transcription within the CA1 field of the hippocampus are associated with age-related spatial learning impairments

Aged rats display a broad range of behavioral performance in spatial learning. The aim of this study was to identify candidate genes that are associated with learning and memory impairments. We first categorized aged-superior learners and age learning-impaired rats based on their performance in the Morris water maze (MWM) and then isolated messenger RNA from the CA1 hippocampal region of each animal to interrogate Affymetrix microarrays. Microarray analysis identified a set of 50 genes that was transcribed differently in aged-superior learners that had successfully learned the spatial strategy in the MWM compared to aged learning-impaired animals that were unable to learn and a variety of groups designed to control for all non-learning aspects of exposure to the water maze paradigm. A detailed analysis of the navigation patterns of the different groups of animals during acquisition and probe trials of the MWM task was performed. Young animals used predominantly an allocentric (spatial) search strategy and aged-superior learners appeared to use a combination of allocentric and egocentric (response) strategies, whereas aged-learning impaired animals displayed thiginotactic behavior. The significant 50 genes that we identified were tentatively classified into four groups based on their putative role in learning: transcription, synaptic morphology, ion conductivity and protein modification. Thus, this study has potentially identified a set of genes that are responsible for the learning impairments in aged rats. The role of these genes in the learning impairments associated with aging will ultimately have to be validated by manipulating gene expression in aged rats. Finally, these 50 genes were functioning in the context of an aging CA1 region where over 200 genes was found to be differentially expressed compared to a young CA1. (c) 2006 Elsevier Inc. All rights reserved.