Miko Curtis

Project: Reward Memories Bias Instrumental Rule Selection via the Orbitofrontal Cortex to Secondary Motor Cortex Pathway

Lab Group: Keiflin Lab

Graduate Mentor: Margo Le

Abstract: Reward-predictive cues can be strongly influential on the selection of actions leading to specific outcomes. In animal models, this is generally studied using the specific Pavlovian-to-Instrumental-Transfer paradigm (s-PIT), in which a reward-predictive cue can elicit a bias towards a discrete action (left or right lever press) directed toward a specific outcome. However, naturalistic processes do not only involve discrete actions, but rather logical sequences of actions that can be hierarchically organized into rules. Thus, the influence of reward cues on rule selection and the underlying circuitry remains largely unknown. The goal of our research is to examine the role that cued reward memories have on rule selection and the neural circuitry involved. To test our hypothesis, we have adapted the s-PIT paradigm to make it more naturalistic and used chemogenetic silencing to assess the role of orbitofrontal projections to the secondary motor cortex (OFC → M2). Preliminary results suggest inhibition of the OFC → M2 pathway significantly disrupts correct cue-biased rule selection. These results identify a potential circuit for therapeutics to target in disorders characterized by impaired cue-based decision-making (schizophrenia, OCD, eating disorders, ADHD, etc.).