Awake functional MRI detects neural circuit dysfunction in a mouse model of autism.
Tomokazu TsurugizawaKota TamadaNobukazu OnoSachise KarakawaYuko KodamaClément S DebackerJunichi HataHideyuki OkanoAkihiko KitamuraAndrew ZaleskyToru TakumiPublished in: Science advances (2020)
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.
Keyphrases
- resting state
- functional connectivity
- wild type
- high fat diet induced
- white matter
- magnetic resonance imaging
- copy number
- mouse model
- contrast enhanced
- autism spectrum disorder
- end stage renal disease
- healthcare
- clinical trial
- computed tomography
- mental health
- diffusion weighted imaging
- ejection fraction
- insulin resistance
- mitochondrial dna
- multiple sclerosis
- stem cells
- deep brain stimulation
- chronic kidney disease
- gene expression
- mesenchymal stem cells
- intellectual disability
- high resolution
- adipose tissue
- patient reported outcomes