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An intra-amygdala circuit specifically regulates social fear learning

Nature Neuroscience volume 20, pages 459469 (2017) | Download Citation

Abstract

Adaptive social behavior requires transmission and reception of salient social information. Impairment of this reciprocity is a cardinal symptom of autism. The amygdala is a critical mediator of social behavior and is implicated in social symptoms of autism. Here we found that a specific amygdala circuit, from the lateral nucleus to the medial nucleus (LA–MeA), is required for using social cues to learn about environmental cues that signal imminent threats. Disruption of the LA–MeA circuit impaired valuation of these environmental cues and subsequent ability to use a cue to guide behavior. Rats with impaired social guidance of behavior due to knockout of Nrxn1, an analog of autism-associated gene NRXN, exhibited marked LA–MeA deficits. Chemogenetic activation of this circuit reversed these impaired social behaviors. These findings identify an amygdala circuit required to guide emotional responses to socially significant cues and identify an exploratory target for disorders associated with social impairments.

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Acknowledgements

The authors thank B. Roth (UNC School of Medicine) for making DREADD constructs available and for advice on immunohistological confirmation of expression. The authors would also like to thank B. Avonts for technical assistance mapping viral injection. Grant support was provided by Simons Foundation (SFARI Award 283746 to J.A.R.) and National Institutes of Health (R01MH084970 to J.A.R.).

Author information

Author notes

    • Robert C Twining
    •  & Jaime E Vantrease

    These authors contributed equally to this work.

Affiliations

  1. Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.

    • Robert C Twining
    • , Jaime E Vantrease
    • , Skyelar Love
    • , Mallika Padival
    •  & J Amiel Rosenkranz

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Contributions

J.E.V. designed experiments to measure mRNA and protein; R.C.T. and J.A.R. designed the remaining experiments. R.C.T., J.E.V., S.L., M.P. and J.A.R. performed all experiments. R.C.T., S.L., J.E.V. and J.A.R. performed statistical analyses. J.A.R. wrote the manuscript with input from all authors. R.C.T. and J.E.V. provided critical revisions.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to J Amiel Rosenkranz.

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https://doi.org/10.1038/nn.4481

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