Brain-wide fMRI responses to auditory and visual stimuli in awake mice

Abstract

Abstract The functions of individual senses are well studied, but the mechanisms of cross-sensory integration remain poorly understood. Although invasive studies in mice can elucidate cellular and circuit-level processes, it is unclear whether mice exhibit macroscale cross-sensory activity comparable to that reported in human imaging studies—an important criterion for the translational relevance of preclinical studies. To address this gap, we investigated responses to unimodal and bimodal auditory and visual stimulation in awake mice using a quiet zero echo time (zero-TE) functional magnetic resonance imaging (fMRI) approach. Both stimulation modalities evoked responses in cross-sensory primary pathways, high-order regions, non-primary thalamus, and cerebellum, indicating robust brain-wide responses to simple sensory stimulation. Bimodal stimulation elicited subadditive responses in regions responsive to both modalities, and primary cortices contained subregions with stronger cross-modal responses. Many of these patterns resembled those observed in humans and non-human primates, suggesting conserved principles across species and supporting the translational value of mechanistic and disease model-oriented studies of cross-sensory processing in mice. In contrast, ketamine-xylazine anesthesia caused widespread suppression of cross-modal and high-order activity during sensory processing, highlighting the importance of performing cross-sensory investigations in awake animals.