RT Journal Article SR Electronic T1 Awake functional MRI detects neural circuit dysfunction in a mouse model of autism JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaav4520 DO 10.1126/sciadv.aav4520 VO 6 IS 6 A1 Tsurugizawa, Tomokazu A1 Tamada, Kota A1 Ono, Nobukazu A1 Karakawa, Sachise A1 Kodama, Yuko A1 Debacker, Clement A1 Hata, Junichi A1 Okano, Hideyuki A1 Kitamura, Akihiko A1 Zalesky, Andrew A1 Takumi, Toru YR 2020 UL http://advances.sciencemag.org/content/6/6/eaav4520.abstract 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.