Article | Published:

Reversing behavioural abnormalities in mice exposed to maternal inflammation

Nature volume 549, pages 482487 (28 September 2017) | Download Citation


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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We thank J. T. Kwon, M. D. Reed, D. Cho, and S. Bigler for assistance with experiments and B. Noro and C. Jennings for critical reading of the manuscript. This work was supported by the Simons Foundation Autism Research Initiative (J.R.H. and D.R.L.), Simons Foundation to the Simons Center for the Social Brain at MIT (Y.S.Y., J.R.H. and G.B.C.), Robert Buxton (G.B.C.), Hock E. Tan and K. Lisa Yang Center for Autism Research (G.B.C.), the DFG grants CRC/TRR 128 project A07 and WA1600/8-1 (A.W.), the Howard Hughes Medical Institute (D.R.L.), the National Research Foundation of Korea grants MEST-35B-2011-E00012 (S.K.) and NRF-2014R1A1A1006089 (H.K.), the Searle Scholars Program (J.R.H.), the Pew Scholar for Biomedical Sciences (J.R.H.), the Kenneth Rainin Foundation (J.R.H.) and the National Institutes of Health grants R01DK106351 and R01DK110559 (J.R.H.).

Author information

Author notes

    • Jun R. Huh

    Present address: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA and Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.


  1. McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Yeong Shin Yim
    • , Ashley Park
    • , Janet Berrios
    • , Mathieu Lafourcade
    • , Leila M. Pascual
    • , Natalie Soares
    • , Joo Yeon Kim
    • , Ian R. Wickersham
    • , Mark T. Harnett
    •  & Gloria B. Choi
  2. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Yeong Shin Yim
    • , Ashley Park
    • , Janet Berrios
    • , Mathieu Lafourcade
    • , Leila M. Pascual
    • , Natalie Soares
    • , Joo Yeon Kim
    • , Mark T. Harnett
    •  & Gloria B. Choi
  3. Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

    • Sangdoo Kim
    • , Hyunju Kim
    •  & Jun R. Huh
  4. Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    • Ari Waisman
  5. Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA

    • Dan R. Littman
  6. Howard Hughes Medical Institute, New York, New York 10016, USA

    • Dan R. Littman


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Y.S.Y., I.R.W., M.T.H., D.R.L., A.W., J.R.H., and G.B.C. designed the experiments and/or provided advice and technical expertise. Y.S.Y., A.P., J.B., M.L., L.M.P., N.S., J.Y.K., S.K., and H.K. performed the experiments. Y.S.Y., J.R.H., and G.B.C. wrote the manuscript with inputs from the co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jun R. Huh or Gloria B. Choi.

Reviewer Information Nature thanks C. Powell, W. Wetsel and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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