期刊
SCIENCE ADVANCES
卷 6, 期 6, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aav4520
关键词
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资金
- Ajinomoto Co. Inc.
- KAKENHI [16H06316, 16H06463, 24700380]
- JST CREST
- Takeda Science Foundation
- Smoking Science Foundation
- Australian National Health and Medical Research Council (NHMRC) [1136649]
- Grants-in-Aid for Scientific Research [24700380] Funding Source: KAKEN
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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