Whole-brain responses to visual and auditory stimuli in anesthetized and minimally restrained awake mice using quiet...

Functional MRI (fMRI) is a flexible tool for sensory perception studies in animal models. However, animal fMRI studies are generally performed under anesthesia. Unfortunately, anesthesia affects brain function and sensory processing, complicating the interpretation of the findings. Since there is a growing need for fMRI protocols applicable for awake animals, we optimized a zero echo time Multi-Band Sweep Imaging with a Fourier Transformation (MB-SWIFT) fMRI approach for imaging awake mice. We implemented a 14-day habituation protocol that resulted in merely moderate motion of the mice while being head-fixed with the animals' body and limbs being free to move. The sensory responsiveness between different states of consciousness was compared by imaging mice with visual and auditory stimulation schemes in the awake state and under ketamine-xylazine anesthesia. In awake mice, we observed a robust whole-brain activation of the ascending auditory and visual pathways, as well as higher sensory processing areas. Under ketamine-xylazine anesthesia, auditory responses were suppressed, and the temporal shapes of fMRI responses were different from those obtained in awake mice. Our results suggest that the quiet and motion-tolerant zero echo time MB-SWIFT approach allows complex behavioral fMRI designs in the awake state that promise to improve our understanding of the underlying mechanisms of perception.