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.

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Sensory processing is a complex neurological process that receives, integrates, and responds to information from one’s own body and environment, which is closely related to survival as well as neurological disorders. Brain-wide networks of sensory processing are difficult to investigate due to their dynamic regulation by multiple brain circuits. Optogenetics, a neuromodulation technique that uses light-sensitive proteins, can be combined with functional magnetic resonance imaging (ofMRI) to measure whole-brain activity. Since ofMRI has increasingly been used for investigating brain circuits underlying sensory processing for over a decade, we systematically reviewed recent ofMRI studies of sensory circuits and discussed the challenges of optogenetic fMRI in rodents.

Pain involves a multidimension network of brain circuits related to both somatosensation and cognitive-motivational dimension. Mouse fMRI allows for the in-vivo brain-wide functional mapping that can help explore the pain circuits at a systems level. We utilized transgenic mice in which we suppressed the anterior cingulate cortex (ACC) with optogenetics to better understand its role in pain. Our behavior and fMRI results show that the ACC is involved in the cognitive-motivational dimension of pain, but not in the sensation of pain. In addition, we detected other brain regions as potential targets related to pain hypersensitivity with fMRI.

It is well known environmental factors can affect brain plasticity in humans, yet finding strong correlative factors is difficult due to the long development and complexity of human research. Mouse enrichment studies allows for better controlled research and by combining it with fMRI, makes mapping brain-wide plasticity changes possible. Here, we treated mice into three groups of enrichment, standard caging, and isolated caging to see how their brain responds to multiple-sensory stimulations. We found the enrichment group responded stronger in multimodal midbrain and thalamic areas. The isolated group responded less suggesting mouse fMRI is viable in detecting plasticity changes.

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