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Chronic stress causes striatal disinhibition mediated by SOM-interneurons in male mice

Author

Listed:
  • Diana Rodrigues

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Luis Jacinto

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Margarida Falcão

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Ana Carolina Castro

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Alexandra Cruz

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Cátia Santa

    (University of Coimbra)

  • Bruno Manadas

    (University of Coimbra)

  • Fernanda Marques

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Nuno Sousa

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

  • Patricia Monteiro

    (University of Minho
    ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimaraes)

Abstract

Chronic stress (CS) is associated with a number of neuropsychiatric disorders, and it may also contribute to or exacerbate motor function. However, the mechanisms by which stress triggers motor symptoms are not fully understood. Here, we report that CS functionally alters dorsomedial striatum (DMS) circuits in male mice, by affecting GABAergic interneuron populations and somatostatin positive (SOM) interneurons in particular. Specifically, we show that CS impairs communication between SOM interneurons and medium spiny neurons, promoting striatal overactivation/disinhibition and increased motor output. Using probabilistic machine learning to analyze animal behavior, we demonstrate that in vivo chemogenetic manipulation of SOM interneurons in DMS modulates motor phenotypes in stressed mice. Altogether, we propose a causal link between dysfunction of striatal SOM interneurons and motor symptoms in models of chronic stress.

Suggested Citation

  • Diana Rodrigues & Luis Jacinto & Margarida Falcão & Ana Carolina Castro & Alexandra Cruz & Cátia Santa & Bruno Manadas & Fernanda Marques & Nuno Sousa & Patricia Monteiro, 2022. "Chronic stress causes striatal disinhibition mediated by SOM-interneurons in male mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35028-4
    DOI: 10.1038/s41467-022-35028-4
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    References listed on IDEAS

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    1. Yuan Mei & Patricia Monteiro & Yang Zhou & Jin-Ah Kim & Xian Gao & Zhanyan Fu & Guoping Feng, 2016. "Adult restoration of Shank3 expression rescues selective autistic-like phenotypes," Nature, Nature, vol. 530(7591), pages 481-484, February.
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