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

Diana Rodrigues, Luis Jacinto, Margarida Falcão, Ana Carolina Castro, Alexandra Cruz, Cátia Santa, Bruno Manadas, Fernanda Marques, Nuno Sousa and Patricia Monteiro ()
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Diana Rodrigues: University of Minho
Luis Jacinto: University of Minho
Margarida Falcão: University of Minho
Ana Carolina Castro: University of Minho
Alexandra Cruz: University of Minho
Cátia Santa: University of Coimbra
Bruno Manadas: University of Coimbra
Fernanda Marques: University of Minho
Nuno Sousa: University of Minho
Patricia Monteiro: University of Minho

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35028-4

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