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.