Adrian Alonso

Reward Memories Bias Instrumental Rule Selection via OFC Projections to M2
Faculty PI: Ron Keiflin

Reward-predictive cues can influence decision-making and promote the pursuit of specific outcomes. This influence is classically studied using specific Pavlovian-to-instrumental transfer (sPIT), in which Pavlovian cues bias action selection and promote the instrumental action (often a left or right lever press) directed toward the cued outcome. However, beyond discrete action selection, reward pursuit often requires selecting abstract rules that organize multiple actions into goal-directed sequences. Whether cued reward memories influence rule selection—and which neural circuits mediate this influence—remains unclear. We adapted sPIT to test how Pavlovian reward cues bias instrumental rule selection and examined the contribution of orbitofrontal cortex projections to secondary motor cortex (OFC→M2) using pathway-specific chemogenetic silencing. Rats expressing hM4Di or mCherry in OFC→M2 neurons learned a three-step instrumental sequence (sample lever–nose poke–choice lever). In alternating blocks, they used either a delayed non-match-to-sample rule to earn one outcome (dNMTS→O1) or a visual-cue rule to earn another (VIS→O2). Rats then learned that two auditory cues predicted these outcomes (S1→O1; S2→O2). During non-rewarded probe tests following DCZ administration, Pavlovian cues biased rule selection in control rats: S1 promoted the dNMTS rule, whereas S2 promoted the visual rule. Chemogenetic inhibition of OFC→M2 neurons abolished this cue-induced bias. In contrast, OFC→M2 inhibition spared conventional sPIT, in which reward-predictive cues directly biased action selection without requiring abstract rules or action sequences. These findings demonstrate that cued reward memories can govern abstract rule selection and identify OFC→M2 as a critical circuit for translating those memories into goal-appropriate behavioral strategies.