Sex-dependent contributions of ventrolateral orbitofrontal cortex and basolateral amygdala to learning under uncertainty.

Inflexible learning is a feature of several neuropsychiatric disorders. We investigated how the ventrolateral orbitofrontal cortex (vlOFC) and basolateral amygdala (BLA) are involved in learning of stimuli or actions under different forms of uncertainty. Following chemogenetic inhibition of these regions in both male and females, we measured detection and adjustment to fully-predictive (i.e., deterministic) and subsequent probabilistic reversals. For action learning, vlOFC and BLA exhibited a sex-dependent role in deterministic and probabilistic learning with females exhibiting the slowest learning following inhibition. For stimulus learning, vlOFC, but not BLA, was required for reversal detection and adjustment. These findings provide insight into the mechanisms of learning under different forms of uncertainty and the sex-dependency of these mechanisms.