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- Title
Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2.
- Authors
Xu, Pan; Yue, Yuanlei; Su, Juntao; Sun, Xiaoqian; Du, Hongfei; Liu, Zhichao; Simha, Rahul; Zhou, Jianhui; Zeng, Chen; Lu, Hui
- 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. Impaired sociability is often interpreted as social avoidance. Here, the authors show that the problem is actually failure to distinguish social from nonsocial stimuli, caused by indistinguishable coactivity patterns in the medial prefrontal cortex.
- Subjects
PYRAMIDAL neurons; RETT syndrome; MICE; SOCIABILITY
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-31578-9