Awake functional MRI detects neural circuit dysfunction in a mouse model of autism
| Autor: | 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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| Rok vydání: | 2018 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities genetic structures Behavior Animal SciAdv r-articles Electroencephalography Mice Transgenic Motor Activity behavioral disciplines and activities Magnetic Resonance Imaging Disease Models Animal Mice Diffusion Tensor Imaging nervous system Neural Pathways Animals Autistic Disorder Nerve Net Wakefulness psychological phenomena and processes Research Articles Research Article Neuroscience |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Awake fMRI detects the hypoconnectivity partially rescued by d-cycloserine treatment in 15q dup mice. 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. |
| Databáze: | OpenAIRE |
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