4.8 Article

Reversing behavioural abnormalities in mice exposed to maternal inflammation

期刊

NATURE
卷 549, 期 7673, 页码 482-+

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/nature23909

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资金

  1. Simons Foundation Autism Research Initiative
  2. Simons Foundation
  3. Hock E. Tan and K. Lisa Yang Center for Autism Research
  4. DFG [CRC/TRR 128, WA1600/8-1]
  5. Howard Hughes Medical Institute
  6. National Research Foundation of Korea [MEST-35B-2011-E00012, NRF-2014R1A1A1006089]
  7. Searle Scholars Program
  8. Pew Scholar for Biomedical Sciences
  9. Kenneth Rainin Foundation
  10. National Institutes of Health [R01DK106351, R01DK110559]

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Viral infection during pregnancy is correlated with increased frequency of neurodevelopmental disorders, and this is studied in mice prenatally subjected to maternal immune activation (MIA). We previously showed that maternal T helper 17 cells promote the development of cortical and behavioural abnormalities in MIA-affected offspring. Here we show that cortical abnormalities are preferentially localized to a region encompassing the dysgranular zone of the primary somatosensory cortex (S1DZ). Moreover, activation of pyramidal neurons in this cortical region was sufficient to induce MIA-associated behavioural phenotypes in wild-type animals, whereas reduction in neural activity rescued the behavioural abnormalities in MIA-affected offspring. Sociability and repetitive behavioural phenotypes could be selectively modulated according to the efferent targets of S1DZ. Our work identifies a cortical region primarily, if not exclusively, centred on the S1DZ as the major node of a neural network that mediates behavioural abnormalities observed in offspring exposed to maternal inflammation.

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