Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear

Abstract

Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsion and compulsive disorders. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented instrumental conditioned punishment learning in a manner that could not be attributed to differences in Pavlovian conditioned fear. We then showed that increasing the frequency of punishing outcomes allowed mOFC-lesioned animals to overcome their initial deficit. Our second experiment demonstrated that the retrieval of instrumental punishment is also mOFC-dependent, as mOFC lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent the re-acquisition of conditioned punishment that was learned prior to lesions being administered. Together, these results reveal that the mOFC does indeed regulate punishment learning and retrieval in a manner that is disassociated from any role in Pavlovian fear learning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.

The medial orbitofrontal cortex - basolateral amygdala circuit regulates the influence of reward cues on adaptive behavior and choice

“…The BLA is heavily implicated in aversive learning and memory (Fanselow and Wassum, 2015;Janak and Tye, 2015). Whether BLAmOFC projections have a similar function in using cues to represent the value of a predicted aversive outcome for adaptive avoidance responses is an intriguing possibility for follow-up exploration, especially given mOFC involvement in aversive motivation (Plassmann et al, 2010;Hsieh and Chang, 2020;Ma et al, 2020;Xie et al, 2021).…”

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“…From this perspective, it may not be surprising that neurons found to encode a given value in classical (i.e., exafferent) situations do not necessarily have to sustain the matching preference in operant (i.e., re-afferent) situations: a classical US is not the same as reinforcement. This distinction can also be observed, e.g., when medial orbitofrontal cortex in rodents regulates operant avoidance but not Pavlovian fear (Ma et al, 2020).…”

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