Multi-connectomics underpin emotional dysfunction in mouse exposed to simulated space composite environment

Long-duration space exploration, including missions to the Moon and Mars, demands strategies to preserve astronauts' emotional well-being for optimal performance. This study combines behavioral phenotyping, multimodal MRI, in vivo calcium imaging, and brain-wide genomics to bridge macroscopic brain function with mesoscopic neural activity and microscopic genetic processes, providing a dynamic characterization of the mouse connectome under simulated spaceflight conditions. We observed a reduction in gray matter volume, particularly in the prefrontal cortex, with prolonged exposure. Simulated space composite environment (SSCE) disrupted multi-scale functional connectivity and altered the macro-organizational functional gradient, reversing the relationship between brain function and emotional behaviors. Neural activity in the medial prefrontal cortex demonstrated exposure-time-dependent changes across emotional tasks, while genetic analyses linked SSCE-induced alterations in functional profiles to synaptic function and ion channel activity. Our findings reveal how extreme environments impact emotional behaviors, brain networks, and neural activity, offering insights for interventions to maintain brain integrity during extended space missions.