Awake functional MRI detects neural circuit dysfunction in a mouse model of autism.

Abstract

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 inmice, a copy number variation model of autism. Compared to wild-type mice, we find thatis 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 inmice, suggesting a putative anatomical substrate for these functional hypoconnectivity. We show that d-cycloserine (DCS) treatment partially normalizes these anormalies in the frontal cortex ofmice and rescues some social behaviors. Our results demonstrate the utility of awake rodent fMRI and provide a rationale for further investigation of DCS therapy.