Lesions of either anterior orbitofrontal cortex or ventrolateral prefrontal cortex in marmoset monkeys heighten innate fear and attenuate active coping behaviors to predator threat

Abstract

The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral prefrontal cortex (vlPFC) and anterior orbitofrontal cortex (antOFC) in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e., human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e., a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied etiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies.

Child Abuse, Neural Structure, and Adolescent Psychopathology: A Longitudinal Study

“…24 Similarly, the OFC is implicated in both emotion regulation and emotion-based decision making, as evidenced by neuroimaging and lesion studies. 25,26 …”

A dimensional approach to modeling symptoms of neuropsychiatric disorders in the marmoset monkey

“…This test is relatively quick to perform, as it is based in the home cage, requires no training and thus is ideal for screening large numbers of animals. Another paradigm to assess emotional reactivity in marmosets is based on the response to a snake, which is a stimulus that primates find inherently fearful [Shiba et al, , b; Fig. (a)].…”

“…At face value, the effects of both lesions seemed almost identical, increasing anxiety as measured by the human intruder test, increasing innate fear in response to a snake stimulus [Fig. (b)] and inducing inflexible conditioned cardiovascular and behavioral fear responses following acute alterations in the pairing of a stimulus with aversive loud noise (Agustín‐Pavón et al, ; Shiba et al, ). This resembles the robust pattern of conditioned fear found in anxiety patients who display stronger responses to conditioned cues during extinction and are delayed in extinguishing responses compared with controls (Wessa and Flor, ; Duits et al, ).…”

Mapping the neural circuitry of predator fear in the nonhuman primate

“…The defensive responses of marmosets to predators in the wild have been described and include visual scanning, alarm calling, mobbing, avoidance, freezing, and flight (13,14). Exposure to toy snakes, cats or raptors have been used in the laboratory setting to induce visual scanning, alarm calling, freezing and threat displays (15–17). However, to the best of our knowledge, the full repertoire of active defensive responses, including flight and post-flight vigilance observed in response to predators in the wild, has not been reported under laboratory conditions.…”