Neural coding of choice and outcome are modulated by uncertainty in orbitofrontal but not secondary motor cortex.

Orbitofrontal cortex (OFC) and secondary motor cortex (M2) are both implicated in flexible reward learning but the conditions that differentially recruit these regions are not fully understood. We imaged calcium activity from single neurons in OFC or M2 during de novo learning of increasingly uncertain reward probability schedules. Predictions of choice were decoded from M2 neurons with high accuracy under all certainty conditions, but were more accurately decoded from OFC neurons under greater uncertainty. The number of choice- and reward-selective neurons was significantly higher in M2 than in OFC across schedules, but these proportions increased across levels of uncertainty only in OFC. Decoding accuracy of choice and outcome was predicted by behavioral strategies Win-Stay and Lose-Shift in OFC, but not M2. We also tested causal involvement of these regions with chemogenetic perturbation as rats learned increasing and then decreasing uncertainty schedules. Whereas inhibition of OFC neurons attenuated learning across all schedules, M2 neurons were found to support learning in the most certain reward schedule. Thus, OFC neurons preferentially encode choices and outcomes that foster a greater reliance on adaptive strategies under uncertainty. This reveals a novel functional heterogeneity within frontal cortex in support of flexible learning.