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Resolving the neural circuits of anxiety

Abstract

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.

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Figure 1: Few new pharmacotherapies for the treatment of anxiety have been developed since the 1940s.
Figure 2: Validated tests to assay anxiety and related emotional states in mice.
Figure 3: Neural circuits implicated in anxiety-related behaviors in the rodent brain.
Figure 4: Circuit organization in anxiety: a problem with interpretation.

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Acknowledgements

We thank M. Kinch and M. Kheirbek for correspondence, C. Vander Weele and R. Wichmann for reading and comments on our text, and the entire Tye laboratory for discussion. K.M.T. is a New York Stem Cell Foundation – Robertson Investigator, and this work was supported by funding from the JPB Foundation, PIIF, PNDRF, JFDP, Whitehall Foundation, Klingenstein Foundation, McKnight Foundation, NARSAD Young Investigator Award, Alfred P Sloan Foundation, New York Stem Cell Foundation, Whitehead Career Development Chair, US National Institutes of Health (NIH) R01-MH102441-01 (National Institute of Mental Health) and NIH Director's New Innovator Award DP2-DK-102256-01 (National Institute of Diabetes and Digestive and Kidney Diseases). G.G.C. is supported by the JFDP Postdoctoral Fellowship from the JPB Foundation.

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Calhoon, G., Tye, K. Resolving the neural circuits of anxiety. Nat Neurosci 18, 1394–1404 (2015). https://doi.org/10.1038/nn.4101

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