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

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          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.

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          Most cited references39

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          Neurons in the orbitofrontal cortex encode economic value.

          Economic choice is the behaviour observed when individuals select one among many available options. There is no intrinsically 'correct' answer: economic choice depends on subjective preferences. This behaviour is traditionally the object of economic analysis and is also of primary interest in psychology. However, the underlying mental processes and neuronal mechanisms are not well understood. Theories of human and animal choice have a cornerstone in the concept of 'value'. Consider, for example, a monkey offered one raisin versus one piece of apple: behavioural evidence suggests that the animal chooses by assigning values to the two options. But where and how values are represented in the brain is unclear. Here we show that, during economic choice, neurons in the orbitofrontal cortex (OFC) encode the value of offered and chosen goods. Notably, OFC neurons encode value independently of visuospatial factors and motor responses. If a monkey chooses between A and B, neurons in the OFC encode the value of the two goods independently of whether A is presented on the right and B on the left, or vice versa. This trait distinguishes the OFC from other brain areas in which value modulates activity related to sensory or motor processes. Our results have broad implications for possible psychological models, suggesting that economic choice is essentially choice between goods rather than choice between actions. In this framework, neurons in the OFC seem to be a good candidate network for value assignment underlying economic choice.
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            Relative reward preference in primate orbitofrontal cortex.

            The orbital part of prefrontal cortex appears to be crucially involved in the motivational control of goal-directed behaviour. Patients with lesions of orbitofrontal cortex show impairments in making decisions about the expected outcome of actions. Monkeys with orbitofrontal lesions respond abnormally to changes in reward expectations and show altered reward preferences. As rewards constitute basic goals of behaviour, we investigated here how neurons in the orbitofrontal cortex of monkeys process information about liquid and food rewards in a typical frontal task, spatial delayed responding. The activity of orbitofrontal neurons increases in response to reward-predicting signals, during the expectation of rewards, and after the receipt of rewards. Neurons discriminate between different rewards, mainly irrespective of the spatial and visual features of reward-predicting stimuli and behavioural reactions. Most reward discriminations reflect the animals' relative preference among the available rewards, as expressed by their choice behaviour, rather than physical reward properties. Thus, neurons in the orbitofrontal cortex appear to process the motivational value of rewarding outcomes of voluntary action.
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              Neurobiology of rodent self-grooming and its value for translational neuroscience.

              Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders--including models of autism spectrum disorder and obsessive compulsive disorder--that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.
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                Author and article information

                Journal
                Cereb Cortex Commun
                Cereb Cortex Commun
                cercorcomms
                Cerebral Cortex Communications
                Oxford University Press
                2632-7376
                2020
                30 July 2020
                30 July 2020
                : 1
                : 1
                : tgaa039
                Affiliations
                [1 ] School of Psychology, University of New South Wales , Sydney, NSW 2052, Australia
                [2 ] Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney , Sydney, NSW 2007, Australia
                [3 ] St. Vincent’s Centre for Applied Medical Research, St. Vincent’s Hospital Sydney Limited, Darlinghurst , Sydney, NSW 2010, Australia
                Author notes
                Address correspondence to Dr. Laura Bradfield, Centre for Neuroscience and Regenerative Medicine, School of Life Sciences, University of Technology Sydney (St. Vincent’s Campus), 405 Liverpool St., Darlinghurst, Sydney, NSW 2010, Australia. Email: laura.bradfield@ 123456uts.edu.au .
                Author information
                http://orcid.org/0000-0003-3921-0745
                Article
                tgaa039
                10.1093/texcom/tgaa039
                8152850
                34296108
                2df9ff42-1fa9-43f7-8ee1-81ecc98d70b8
                © The Author(s) 2020. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 May 2020
                : 23 July 2020
                : 23 July 2020
                Page count
                Pages: 13
                Funding
                Funded by: Australian Research Council, DOI 10.13039/501100000923;
                Award ID: 200102445
                Funded by: National Health & Medical Research Council of Australia;
                Award ID: 1148244
                Categories
                Original Article

                conditioned punishment,medial orbitofrontal cortex,passive avoidance,pavlovian conditioned fear

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