4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-35028-4

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Chronic stress can trigger or worsen motor symptoms in neuropsychiatric disorders, and SOM interneurons in the striatum are involved in stress-induced motor behaviors.
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. Chronic stress can trigger or worsen motor symptoms in neuropsychiatric disorders. Here, the authors show that SOM interneurons in the striatum are involved in stress-induced motor behaviors.

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