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GABA neurons of the ventral periaqueductal gray area modulate behaviors associated with anxiety and conditioned fear

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Abstract

Emotional behavioral responses related to anxiety and fear comprise the negative valence systems domain as defined by the Research Domain Criteria (RDoC) approach to categorizing related emotional behavioral constructs that are compromised in mental health disorders. Here, we evaluate the role of GABA neurons of the ventral periaqueductal gray (vPAG) in emotional behavioral responses related to anxiety and fear using a chemogenetic approach in Vgat-ires-Cre mice. Functional inhibition of vPAG GABA neurons using selective expression of inhibitory Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADDs) enhanced anxiety-like behavior in the light–dark exploration and open-field tests. Functional inhibition of vPAG GABA neurons during the acquisition of conditioned fear impaired later performance of conditioned fear responses to the fear-associated context. No effects on spontaneous freezing behavior, fear generalization, or conditioned fear responses to the fear-associated cue were observed. Together, these data suggest that activity of vPAG GABA neurons underlies emotional behavioral responses related to anxiety and conditioned fear. As such, vPAG GABA neurons are a common neurophysiological correlate of the negative valence system and dysregulation of this population may contribute to the etiology of mental health disorders in which the negative valence systems domain is compromised.

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Acknowledgements

The authors have no conflicts of interest to declare. This work was supported by the Bowles Center for Alcohol Studies and NIAAA/ NIH: F32-AA022549 (E.G.L.G.); T32-AA007573; R01-AA019454 (T.L.K.); U01-AA020911 (T.L.K.); and P60-AA011605.

Funding

This work was supported by the Bowles Center for Alcohol Studies and NIAAA/ NIH: F32-AA022549 (E.G.L.G.); T32-AA007573; R01-AA019454 (T.L.K.); U01-AA020911 (T.L.K.); and P60-AA011605.

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Correspondence to Emily G. Lowery-Gionta.

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The authors have no potential conflicts of interest to disclose.

Research involving human participants and/or animals

All procedures used in the current study were approved by the University of North Carolina at Chapel Hill’s Institutional Animal Care and Use Committee and follow the NIH ethical guidelines for the use of animal subjects in research.

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All procedures used in the current study were approved by the University of North Carolina at Chapel Hill’s Institutional Animal Care and Use Committee and follow the NIH ethical guidelines for the use of animal subjects in research.

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Informed consent is not applicable for any studies herein.

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Lowery-Gionta, E.G., DiBerto, J., Mazzone, C.M. et al. GABA neurons of the ventral periaqueductal gray area modulate behaviors associated with anxiety and conditioned fear. Brain Struct Funct 223, 3787–3799 (2018). https://doi.org/10.1007/s00429-018-1724-z

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  • DOI: https://doi.org/10.1007/s00429-018-1724-z

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