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Mouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.

Characterization of brain-wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and ketamine/xylazine