The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats. Interestingly, we found that inactivation of the orbitofrontal cortex (OFC), but not the dorsal or ventral medial prefrontal cortices, blocked retrieval of choice CTA. However, OFC inactivation left retrieval of no-choice CTA intact, suggesting its role in guiding choice, but not in retrieval of CTA memory. Consistently, OFC activity increased in the choice condition compared with no-choice, as measured with c-Fos immunolabeling. Notably, OFC inactivation did not affect choice behavior when it was guided by innate taste aversion. Consistent with an anterior insular cortex (AIC) involvement in storing taste memories, we found that AIC inactivation impaired retrieval of both choice and no-choice CTA. Therefore, this study provides evidence for OFC's role in guiding choice behavior and shows that this is dissociable from AIC-dependent taste aversion memory. Together, our results suggest that OFC is required and recruited to guide choice selection between options of taste associations relayed from AIC.
SIGNIFICANCE STATEMENT Survival and mental health depend on being able to choose stimuli not associated with danger. This is particularly important when danger is associated with stimuli that we ingest. Although much is known about the brain mechanisms that underlie associations with dangerous taste stimuli, very little is known about how these stored emotional associations guide behavior when it involves choice. By combining pharmacological and immunohistochemistry tools with taste-guided tasks, our study provides evidence for the key role of orbitofrontal cortex activity in choice behavior and shows that this is dissociable from the adjacent insular cortex-dependent taste aversion memory. Understanding the brain mechanisms that underlie the impact that emotional associations have on survival choice behaviors may lead to better treatments for mental disorders characterized by emotional decision-making deficits.