Awake functional MRI detects neural circuit dysfunction in a mouse model of autism

Tomokazu Tsurugizawa, Kota Tamada, Nobukazu Ono, Sachise Karakawa, Yuko Kodama, Clement Debacker, Junichi Hata, Hideyuki Okano, Akihiko Kitamura, Andrew Zalesky, Toru Takumi

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Abstract

MRI has potential as a translational approach from rodents to humans. However, given that mouse functional MRI (fMRI) uses anesthetics for suppression of motion, it has been difficult to directly compare the result of fMRI in “unconsciousness” disease model mice with that in “consciousness” patients. We develop awake fMRI to investigate brain function in 15q dup mice, a copy number variation model of autism. Compared to wild-type mice, we find that 15q dup is associated with whole-brain functional hypoconnectivity and diminished fMRI responses to odors of stranger mice. Ex vivo diffusion MRI reveals widespread anomalies in white matter ultrastructure in 15q dup mice, suggesting a putative anatomical substrate for these functional hypoconnectivity. We show that d-cycloserine (DCS) treatment partially normalizes these anormalies in the frontal cortex of 15q dup mice and rescues some social behaviors. Our results demonstrate the utility of awake rodent fMRI and provide a rationale for further investigation of DCS therapy.

Original languageEnglish
Article numbereaav4520
JournalScience Advances
Volume6
Issue number6
DOIs
Publication statusPublished - 2020 Feb 5

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Tsurugizawa, T., Tamada, K., Ono, N., Karakawa, S., Kodama, Y., Debacker, C., Hata, J., Okano, H., Kitamura, A., Zalesky, A., & Takumi, T. (2020). Awake functional MRI detects neural circuit dysfunction in a mouse model of autism. Science Advances, 6(6), [eaav4520]. https://doi.org/10.1126/sciadv.aav4520