RESUMEN
Increases in performance on tests of attention and learning are often observed shortly after a period of aerobic exercise, and evidence suggests that humans who engage in regular exercise are partially protected from age-related cognitive decline. However, the cognitive benefits of exercise are typically short-lived, limiting the practical application of these observations. Here, we explored whether physical exercise might induce lasting changes in general cognitive ability if that exercise was combined with working memory training, which is purported to broadly impact cognitive performance. Mice received either exercise treatment (6 weeks of voluntary running wheel access), working memory training (in a dual radial-arm maze), both treatments, or various control treatments. After this period of exercise, working memory training was initiated (alternating with days of exercise), and continued for several weeks. Upon completion of these treatments, animals were assessed (2-4 weeks later) for performance on four diverse learning tasks, and the aggregate performance of individual animals across all four learning tasks was estimated. Working memory training alone promoted small increases in general cognitive performance, although any beneficial effects of exercise alone had dissipated by the time of learning assessments. However, the two treatments in combination more than doubled the improvement in general cognitive performance supported by working memory training alone. Unlike the transient effects that acute aerobic exercise can have on isolated learning tasks, these results indicate that an acute period of exercise combined with working memory training can have synergistic and lasting impact on general cognitive performance.
Asunto(s)
Cognición/fisiología , Aprendizaje por Laberinto/fisiología , Memoria a Corto Plazo/fisiología , Condicionamiento Físico Animal/fisiología , Carrera/fisiología , Animales , Reacción de Prevención/fisiología , Aprendizaje Discriminativo/fisiología , RatonesRESUMEN
BACKGROUND: Genetically heterogeneous mice express a trait that is qualitatively and psychometrically analogous to general intelligence in humans, and as in humans, this trait co-varies with the processing efficacy of working memory (including its dependence on selective attention). Dopamine signaling in the prefrontal cortex (PFC) has been established to play a critical role in animals' performance in both working memory and selective attention tasks. Owing to this role of the PFC in the regulation of working memory, here we compared PFC gene expression profiles of 60 genetically diverse CD-1 mice that exhibited a wide range of general learning abilities (i.e., aggregate performance across five diverse learning tasks). METHODOLOGY/PRINCIPAL FINDINGS: Animals' general cognitive abilities were first determined based on their aggregate performance across a battery of five diverse learning tasks. With a procedure designed to minimize false positive identifications, analysis of gene expression microarrays (comprised of ≈25,000 genes) identified a small number (<20) of genes that were differentially expressed across animals that exhibited fast and slow aggregate learning abilities. Of these genes, one functional cluster was identified, and this cluster (Darpp-32, Drd1a, and Rgs9) is an established modulator of dopamine signaling. Subsequent quantitative PCR found that expression of these dopaminergic genes plus one vascular gene (Nudt6) were significantly correlated with individual animal's general cognitive performance. CONCLUSIONS/SIGNIFICANCE: These results indicate that D1-mediated dopamine signaling in the PFC, possibly through its modulation of working memory, is predictive of general cognitive abilities. Furthermore, these results provide the first direct evidence of specific molecular pathways that might potentially regulate general intelligence.