Previously, we have reported the existence of a general learning factor in genetically heterogeneous mice, and this factor is in many ways analogous to general intelligence in humans. This previous work established that the processes underlying general learning abilities in mice are, as in humans, related to working memory capacity and specifically selective attention. In the present set of experiments, using gene-expression microarray technology that allowed us to quantify the expression of

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... ,000 genes simultaneously, we assessed the gene expression profiles of the best and worst learners from a sample of 60 mice (in two replications). For each group we compared four different brain regions (prefrontal cortex, the remaining cortex, cerebellum and hippocampus). The most consistent pattern of differential expression was found in the prefrontal cortex, here a set of genes associated with the efficacy of dopamine functioning (i.e., Drd1a, Darpp-32, Rgs9) were upregulated in the fastest learners. As prefrontal dopamine functioning is associated with working memory, these results dove-tail with our previous behavioral results that demonstrated a relationship between working memory capacity and general learning abilities. This relationship was further verified through a quantitative PCR analysis where we demonstrated a significant correlation between the expression of these prefrontal dopamine genes and the general learning abilities of 48 mice. In total these results suggest that working memory and specifically dopamine signaling efficacy in the prefrontal cortex may be crucial for the establishment of general learning abilities.