Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2

Pan Xu, Yuanlei Yue, Juntao Su, Xiaoqian Sun, Hongfei Du, Zhichao Liu, Rahul Simha, Jianhui Zhou, Chen Zeng and Hui Lu ()
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Pan Xu: The George Washington University
Yuanlei Yue: The George Washington University
Juntao Su: The George Washington University
Xiaoqian Sun: The George Washington University
Hongfei Du: The George Washington University
Zhichao Liu: The George Washington University
Rahul Simha: The George Washington University
Jianhui Zhou: University of Virginia
Chen Zeng: The George Washington University
Hui Lu: The George Washington University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Sociability is crucial for survival, whereas social avoidance is a feature of disorders such as Rett syndrome, which is caused by loss-of-function mutations in MECP2. To understand how a preference for social interactions is encoded, we used in vivo calcium imaging to compare medial prefrontal cortex (mPFC) activity in female wild-type and Mecp2-heterozygous mice during three-chamber tests. We found that mPFC pyramidal neurons in Mecp2-deficient mice are hypo-responsive to both social and nonsocial stimuli. Hypothesizing that this limited dynamic range restricts the circuit’s ability to disambiguate coactivity patterns for different stimuli, we suppressed the mPFC in wild-type mice and found that this eliminated both pattern decorrelation and social preference. Conversely, stimulating the mPFC in MeCP2-deficient mice restored social preference, but only if it was sufficient to restore pattern decorrelation. A loss of social preference could thus indicate impaired pattern decorrelation rather than true social avoidance.

Date: 2022
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DOI: 10.1038/s41467-022-31578-9

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