Identification of learning and aging associated genes rat hippocampus and other brain regions. To assess changes in gene expression associated with learning and memory processes, we have used cDNA microarray to analyze hippocampal gene expression in male Fischer-344 rats following training in a 14-unit T-maze, (Stone maze), a task that is dependent on normal hippocampal function. Through a sequential analysis involving large-scale commercial filters (over 15,000 unique cDNA clones) and a custom-made filter (consisting of 1,124 cDNA selected clones), we have identified 28 unique cDNA clones (18 known genes and 10 ESTs) whose expression was enhanced in rat hippocampus following Stone maze learning. Some of those genes appear to be involved in calcium signaling, Ras activation, kinase cascades, and extracellular matrix function, suggesting that these genes may function in regulating neural transmission, synaptic plasticity, and neurogenesis. All those events are believed to be essential elements in learning and memory processes. The analysis of gene expression profile provides the groundwork for future, more focused research to elucidate the contribution of these genes in learning and memory processes. We are currently conducting a large-scale gene expression analysis of rat hippocampus and other brain regions during aging (rats aged at 1, 6, 16, and 24 month old). In parallel, we analyze rats under caloric restriction, a model that has been shown to increase quality and longevity of rats. We use cDNA filters containing 15,000 unique clones isolated from mouse embryos and containing 9,000 unique clones isolated mainly from mouse hippocampus, front cortex, and cerebellum. We will carry out independent array experiments of 3-4 individual rats from each age group. Such analysis will allow us to assess age-associated gene expression changes in normal as well as caloric restricted rats.
