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Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4075-E4084. doi: 10.1073/pnas.1620115114. Epub 2017 May 1.

Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion.

Author information

1
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom.
2
Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
3
Department of Psychiatry, University of Cambridge, Cambridge CB2 OQQ, United Kingdom.
4
Liaison Psychiatry Service, Cambridge and Peterborough National Health Service Foundation Trust, Cambridge CB2 OQQ, United Kingdom.
5
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom; hfc23@cam.ac.uk.

Abstract

Disorders of dysregulated negative emotion such as depression and anxiety also feature increased cardiovascular mortality and decreased heart-rate variability (HRV). These disorders are correlated with dysfunction within areas 25 and 32 of the ventromedial prefrontal cortex (vmPFC), but a causal relationship between dysregulation of these areas and such symptoms has not been demonstrated. Furthermore, cross-species translation is limited by inconsistent findings between rodent fear extinction and human neuroimaging studies of negative emotion. To reconcile these literatures, we applied an investigative approach to the brain-body interactions at the core of negative emotional dysregulation. We show that, in marmoset monkeys (a nonhuman primate that has far greater vmPFC homology to humans than rodents), areas 25 and 32 have causal yet opposing roles in regulating the cardiovascular and behavioral correlates of negative emotion. In novel Pavlovian fear conditioning and extinction paradigms, pharmacological inactivation of area 25 decreased the autonomic and behavioral correlates of negative emotion expectation, whereas inactivation of area 32 increased them via generalization. Area 25 inactivation also increased resting HRV. These findings are inconsistent with current theories of rodent/primate prefrontal functional similarity, and provide insight into the role of these brain regions in affective disorders. They demonstrate that area 32 hypoactivity causes behavioral generalization relevant to anxiety, and that area 25 is a causal node governing the emotional and cardiovascular symptomatology relevant to anxiety and depression.

KEYWORDS:

depression; fear conditioning; marmoset; negative emotion; vmPFC

PMID:
28461477
PMCID:
PMC5441783
DOI:
10.1073/pnas.1620115114
[Indexed for MEDLINE]
Free PMC Article

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