Interdisciplinary Initiatives Program Round 6 - 2012

Brian Knutson, Psychology
Karl Deisseroth, Bioengineering

By combining optogeneticswith neuroimaging across species, we propose to causally deconstruct the neural substrates of risky choice. Modern neuroimaging techniques (like functional magnetic resonance imaging or FMRI) have allowed investigators to visualize neural activity during the anticipation of good and bad outcomes, as well as to use this activity to predict upcoming choice (Knutson & Bossaerts, 2007). Consistent with an "anticipatory affect" account, FMRI research in humans suggests that while increased nucleus accumbens (NAcc) activation precedes and promotes risk seeking, increased anterior insula (AI) activation instead precedes and promotes risk avoidance. However, little is known about which physiological events generate this activity, or whether they exert a causal impact on choice. Based on the hypothesis that biogenic amines (Le., dopamine and norepinephrine) differentially contribute to FMRI activity in the NAcc and AI, we propose to combine targetedoptogenetic manipulations with FMRI in rats to determine: (1) the separate and combined quantitative impacts of dopamine and norepinephrine firingonFMRI Signal in the NAcc and AI; (2) the separate and combined impacts of dopamine and norepinephrine firing on risk seeking and risk avoidant choice, and (3) whether observed FMRI activity can account for the relationship between optogenetically induced amine release and behavioral shifts in risky choice. Findings promise to bridge species, physiological substrates, and academic disciplines. Resulting knowledge should lay the foundation for a physiologically grounded, causal, and predictive theory of choice, which may account for a broad range of behaviors ranging from foraging tofinancial decision making.