Evidence of a role for orbital prefrontal cortex in preventing over-generalization to moderate predictors of biologically significant events

Abstract

The mammalian brain is specialized to acquire information about environmental predictors of biologically significant events. However, environments contain an array of stimuli from which animals must ascertain which ones are meaningful in the current situation. This kind of uncertainty is inherent in the discriminative fear conditioning to context task (DFCTC) during which rats are trained to associate one context with foot-shock and another distinct context with no event. Although the contexts differ on several dimensions, they also share similarities making some cues perfect predictors, but others moderate predictors. Appropriate responding requires animals to determine which cues are relevant in the current situation and the ability to constrain their responses only to those perfect predictors. The orbital prefrontal cortex (OPFC) is thought to modulate this function as OPFC lesions result in over-generalization during DFCTC. Two experiments were conducted; the first was intended to dissociate the role of the OPFC in acquisition and expression of DFCTC, and the second intended to determine if the OPFC will also function to constrain responses during an appetitive version of DFCTC. We found that inactivation of the OPFC prior to assessment measures resulted in generalized responses on the appetitive and aversive task, however, these effects may be more prominent during the aversive task. Despite generalization during activity testing, rats were able to discriminate between the two contexts during preference. These results point to a broader role for the OPFC constraining responses to perfect predictors of biologically significant events in uncertain contexts.