title: A dopaminergic gene cluster in the prefrontal cortex predicts performance indicative of general intelligence in genetically heterogeneous mice.
abstract: 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).
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Psychology, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kolata
authors.forename: Kenneth
authors.initials: K
authors.lastname: Light
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Wass
authors.forename: Danielle
authors.initials: D
authors.lastname: Colas-Zelin
authors.forename: Debasri
authors.initials: D
authors.lastname: Roy
authors.forename: Louis D
authors.initials: LD
authors.lastname: Matzel
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007360:Intelligence; D007858:Learning / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D025341:Principal Component Analysis; D020710:RGS Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D004298:Dopamine