An individual's performance across diverse tests of cognitive ability tends to co-vary, indicative of a common source of underlying variance (i.e., "general intelligence"). Recent evidence indicates that the processing efficacy of working memory predicts the level of general intelligence in humans and general cognitive abilities (GCA) in non-human animals (e.g. rodents and monkeys). One component of working memory, namely selective attention, has been reported to highly co-vary with general

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... lligence, and evidence suggests that dopamine D1 signaling in the medial prefrontal cortex (mPFC) critically modulates attentional abilities. Here, we characterized the GCA of 48 CD-1 outbred mice based on their aggregate performance across five diverse tests of learning. Using immunohistochemical techniques following administration of a D1 agonist (SKF82958, 1 mg/kg), we examined the relationship between GCA and endogenous sensitivity of D1 receptors in the mPFC, the dlPFC, and the striatum. Results indicate a differential sensitivity of D1 receptors in the mPFC (but not the dlPFC or striatum) between animals of high GCA and low GCA (quantified by cFos activation in response to the D1 agonist). In Experiment 2, we assessed whether the enhancement in D1 receptor sensitivity levels were the result of an increased amount of D1 receptors in the mPFC. Results indicated that animals of high GCA and low GCA express no differences in the density of D1 receptors in the mPFC. Subsequently we examined whether the imposition of a working memory training regimen (with a high demand on selective attention) modulates the same dopaminergic signaling mechanisms that were associated with innate GCA. Working memory training promoted an increase in animals' GCA and enhanced the sensitivity of D1 receptors in the mPFC. These findings suggest that the sensitivity (but not number) of D1 receptors in the mPFC may both regulate GCA and may be a target for working memory training that promotes GCA.