TY - JOUR
T1 - Awake functional MRI detects neural circuit dysfunction in a mouse model of autism
AU - Tsurugizawa, Tomokazu
AU - Tamada, Kota
AU - Ono, Nobukazu
AU - Karakawa, Sachise
AU - Kodama, Yuko
AU - Debacker, Clement
AU - Hata, Junichi
AU - Okano, Hideyuki
AU - Kitamura, Akihiko
AU - Zalesky, Andrew
AU - Takumi, Toru
N1 - Funding Information:
We are grateful to F. Kato (The Jikei University School of Medicine), E. Kuwazawa, and T. Tokita (Animal Support Kobe, Kobe, Japan) for technical assistance with the MRI measurements, and we thank K. Torii (Torii Nutrient-State Institute Inc.) for valuable comments for this study. Funding: This work was funded by Ajinomoto Co. Inc.; KAKENHI Grant-in-Aid for Young Scientists, Scientific Research (S), and Scientific Research on Innovative Areas (16H06316, 16H06463, and 24700380); JST CREST; and the Takeda Science Foundation and Smoking Science Foundation. A.Z. was supported by the Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship B (ID: 1136649). Author
Publisher Copyright:
Copyright © 2020 The Authors
PY - 2020/2/5
Y1 - 2020/2/5
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.aav4520
DO - 10.1126/sciadv.aav4520
M3 - Article
C2 - 32076634
AN - SCOPUS:85079103153
VL - 6
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 6
M1 - eaav4520
ER -