title: Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training.
abstract: A common source of variance (i.e., "general intelligence") underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to co-vary with general intelligence, and dopamine D1 signaling in prefrontal cortex can modulate attentional abilities. Based on their aggregate performance across five diverse tests of learning, here we characterized the general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum. Increased activation of D1R-containing neurons in the prelimbic cortex (but not the agranular insular cortex or dorsomedial striatum) was observed in animals of high GCA relative to those of low GCA (quantified by c-Fos activation in response to the D1 agonist). However, a Western blot analysis revealed no differences in the density of D1Rs in the prelimbic cortex between animals of high and low GCA. Last, it was observed that working memory training promoted an increase in animals' GCA and enhanced D1R-mediated neuronal activation in the prelimbic cortex. These results suggest that the sensitivity (but not density) of D1Rs in the prelimbic cortex may both regulate GCA and be a target for working memory training.
authors.affiliation: Department of Psychology, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wass
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pizzo
authors.forename: Bruno
authors.initials: B
authors.lastname: Sauce
authors.forename: Yushi
authors.initials: Y
authors.lastname: Kawasumi
authors.forename: Tudor
authors.initials: T
authors.lastname: Sturzoiu
authors.forename: Fred
authors.initials: F
authors.lastname: Ree
authors.forename: Tim
authors.initials: T
authors.lastname: Otto
authors.forename: Louis D
authors.initials: LD
authors.lastname: Matzel
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; C071262:SK&F 82958