Prefrontal cortex neural compensation during an operant devaluation task

Deficits in goal-directed action are reported in multiple neuropsychiatric conditions, including schizophrenia. However, dysfunction is not always apparent in early stages of schizophrenia, possibly due to neural compensation. We designed a novel devaluation task in which goal-directed action could be guided by stimulus-outcome (S-O) [presumably orbitofrontal cortex (OFC)-mediated] or response-outcome (R-O) associations [presumably prelimbic cortex (PL)-mediated]. We previously found suggestive evidence that OFC and PL could compensate for each other in this task, and we more directly assessed this potential compensation here. In Experiment 1, rats received OFC, PL, combined OFC+PL, or sham lesions and then completed our devaluation task. The OFC+PL lesion group exhibited impaired devaluation. In Experiment 2, rats received cholera-toxin-b (CTb) into OFC and either neurotoxic or sham PL lesions. Rats were then sacrificed on the last training day to double-label for Arc and CTb. We found increased Arc+CTb in mediodorsal thalamus (MD) and increased Arc+ neurons in OFC when PL was lesioned, suggesting that PL lesions lead to a compensatory increased activation of the MD[->]OFC circuit. Our results suggest that our devaluation task can model neural compensation between OFC and PL and this compensation may be regulated by MD. Significance StatementTo detect compensatory responses, behavioral models that use different strategies must be developed to determine if the strategies shift when a brain area or circuit is incapacitated. Neural compensation is commonly observed in human research but only a few models of neural compensation exist, and few identify compensation within the prefrontal cortex. This research is among the first to show neural compensation between prefrontal cortex regions and implicate a thalamocortical circuit in modulating this compensation. Not only will this model provide a way to behaviorally identify subtle neurological shifts, it can also elucidate basic neurological mechanisms that mediate how circuits interact with each other and how dysfunction in one circuit can affect connectivity in other brain areas.