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Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory
Leonardo Fazio1,2,3, Giulio Pergola1,3, Marco Papalino1
1Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, 70124 Bari, Italy.
Summary
Genetic factors influencing dopamine D1 receptor (DRD1) coexpression in the prefrontal cortex are linked to working memory performance and brain activity.
Area of Science:
- Neuroscience
- Genetics
- Cognitive Science
Background:
- Dopamine D1 receptor (D1R) signaling is crucial for prefrontal cortex (PFC) function in working memory (WM).
- Previous research linked higher WM performance to genetic variations associated with increased DRD1 gene expression.
- The role of DRD1's molecular environment and its genetic modulation on PFC activity during WM remains underexplored.
Purpose of the Study:
- To investigate the relationship between a genetically predicted coexpression network involving DRD1 and PFC activity during WM.
- To determine if this network influences WM performance in healthy individuals.
- To identify potential genetic targets for cognitive enhancement strategies.
Main Methods:
- Utilized three independent postmortem prefrontal mRNA datasets (n=404) to identify a DRD1 coexpression network.
- Developed a polygenic coexpression index for DRD1 (DRD1-PCI) using single nucleotide polymorphisms (SNPs) to quantify network coexpression.
- Associated DRD1-PCI with WM performance and PFC activity in independent healthy participant samples (n=371) using behavioral and neuroimaging data.
Main Results:
- Identified and replicated a coexpression network including DRD1, with coexpression levels correlating with DRD1-PCI.
- Found that higher DRD1-PCI was associated with reduced PFC activity during WM tasks.
- Demonstrated that higher DRD1-PCI correlated with enhanced WM performance, with findings replicated across independent samples.
Conclusions:
- Genetically predicted expression of DRD1 and its coexpressed partners influences individual differences in WM performance and associated PFC activity.
- The study highlights specific genes and SNPs that could be relevant for developing pharmacological interventions targeting DRD1 signaling for cognitive enhancement.
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