Abstract
In both humans and mice, performance on tests of intelligence or general cognitive ability (GCA) is related to dopamine D1 receptor-mediated activity in the prelimbic cortex, and levels of DRD1 mRNA predict the GCA of mice. Here we assessed the turnover rate of D1 receptors as well as the expression level of the D1 chaperone protein (DRiP78) in the medial PPC (mPFC) of mice to determine whether rate of receptor turnover was associated with variations in the GCA of genetically heterogeneous mice. Following assessment of GCA (aggregate performance on four diverse learning tests) mice were administered an irreversible dopamine receptor antagonist (EEDQ), after which the density of new D1 receptors were quantified. GCA was positively correlated with both the rate of D1 receptor recovery and levels of DRiP78. Additionally, the density of D1 receptors was observed to increase within 60 min (or less) in response to intense demands on working memory, suggesting that a pool of immature receptors was available to accommodate high cognitive loads. These results provide evidence that innate general cognitive abilities are related to D1 receptor turnover rates in the prefrontal cortex, and that an intracellular pool of immature D1 receptors are available to accommodate cognitive demands.
Highlights
Among humans, 40–50% of the variance of individuals’ performance across diverse cognitive tasks can be accounted for by a single “general” influence[1,2]
Mice with high general cognitive abilities (GCA) exhibit increased neuronal activation in the medial prefrontal cortexl (mPFC) in response to D1 agonists[18]. These results suggest that general cognitive performance, working memory, and dopamine signaling in the prefrontal cortex (PFC) are related, and comprise a system that contributes to variations in intelligence[19,20,21]
It is plausible that animals expressing high GCAs have an increased rate of receptor turnover which would re-sensitize the cell at a faster rate, requiring an increased rate of receptor synthesis
Summary
40–50% of the variance of individuals’ performance across diverse cognitive tasks can be accounted for by a single “general” influence[1,2]. Mice with high GCA exhibit increased neuronal activation in the mPFC in response to D1 agonists[18] In combination, these results suggest that general cognitive performance, working memory, and dopamine signaling in the PFC are related, and comprise a system that contributes to variations in intelligence[19,20,21]. The Drd1a gene is upregulated and the responsivity of D1 receptors is elevated in animals that express high GCA, previous work has not detected a corresponding increase in membrane-bound D1 protein in the PFC18, suggesting that the number of mature D1 receptors does not contribute to variations in GCA. Variations in the rate of protein turnover could contribute to the efficacy of D1 signaling, as newly inserted receptors increase the cell’s response to dopamine[24]. It is plausible that animals expressing high GCAs have an increased rate of receptor turnover which would re-sensitize the cell at a faster rate, requiring an increased rate of receptor synthesis (accommodated by the increase in Drd1A mRNA)
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