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

Cassandra Ma,Simon Killcross,Bryce Vissel,Bernard W Balleine,Philip Jean-Richard-Dit-Bressel,Laura A Bradfield,Stephanie Roughley

doi:10.1093/texcom/tgaa039

Abstract

Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. 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 rats from learning to avoid a lever that was punished with a stimulus that coterminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from reacquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.

Highlights

Aberrant medial orbitofrontal cortical activity has been consistently linked with compulsion and compulsive disorders
It appears from these figures that the increase in reinforcement was sufficient for group medial orbitofrontal cortical (mOFC) to overcome their initial impairment because they, like group SHAM, responded selectively to the unpunished lever and avoided the punished lever
Together, current results demonstrate a causal role for mOFC in instrumental punishment avoidance, but not Pavlovian conditioned fear

Summary

Introduction

Aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsion and compulsive disorders. There are relatively few studies of medial orbitofrontal cortex (OFC) function in rodents, despite its homologous region (i.e. mOFC, which can comprise anything from the more general ventral medial prefrontal cortex to the more specific Brodman’s Area 13) being of intense interest in human studies This interest has arisen, in part, because aberrant activity in mOFC has been consistently identified in individuals with compulsive disorders, such as substance use disorder and obsessive-compulsive disorder (OCD) (Fineberg et al 2011; Fettes et al 2017; Moorman 2018). An individual with OCD might continue to wash their hands despite developing painful sores Such disorders are, complex and multifaceted, and their neural underpinnings intricate, ascertaining the causal consequences of aberrance in one part of this circuit (here, mOFC) for punishment sensitivity could provide insight into why mOFC activity is broadly aberrant across different compulsive disorders that share this core characteristic. To test these hypotheses we compared animals with sham and excitotoxic lesions of the mOFC on several variants of a conditioned punishment procedure (Killcross et al 1997), as this is a unique procedure which allows for a fully dissociated assessment of punishment-driven (instrumental) and fear-driven (Pavlovian) suppression of responding

Methods

Results

Conclusion