Attention, impulsivity and monoamines (AIM)

Substantial insights have also been obtained by studying rodents in the 5-choice serial reaction time task (5CSRTT) invented by co-applicant, Brain Prize winner Trevor Robbins. Despite this progress, there is still a wide gap between our psychological understanding of attention and impulsivity and basic brain mechanisms. We propose, therefore, to bring together experts in basic neuroscience, rodent behavior and psychological modeling in a concerted effort aimed at linking neuronal signaling events in mice to psychological functions in humans. We will focus on dopamine (DA) and norepinephrine (NE), two transmitters known to play important but still poorly understood roles in attention and impulsivity. We hypothesize that human profiles of attention and impulsivity can be directly compared to behavioral parameters obtained in mice by a novel combination of TVA-based modeling and the 5CSRTT. Parallel studies will be done in humans and mice to assess the effects of pharmacological challenges of the DA and NE systems and behavioral models will be refined to improve translation across species. Moreover, we will employ advanced viral expression methods, together with a multiplexed, chemogenetic approach (“DREADDs”). This will permit independent pharmacological silencing of neuronal populations and thereby disentangle how DA and NE neural circuits work co-operatively or competitively to control translatable cognitive parameters. Altogether, the project should deliver a novel translational understanding of the biology underlying attention and impulsivity with direct relevance for disorders characterized by impaired attention such as ADHD.