Dissecting the Strain and Sex Specific Connectome Signatures of Unanesthetized <scp>C57BL</scp> / <scp>6J</scp> and <scp>DBA</scp> / <scp>2J</scp> Mice Using Magnetic Resonance Imaging

ABSTRACT Mouse models are an essential tool for understanding behavior and disease states in neuroscience research. While genetic and sex‐specific effects have been reported in many neurodegenerative and psychiatric illnesses, these factors may also alter baseline neuroanatomical features of mice. This raises the question of whether the observed changes are related to the disease being studied (i.e., pathological differences) or if there are baseline strain or sex differences that may predispose animals to different responses. Over the past decade, tremendous effort has been made to map neural architecture at various scales; however, the complex relationships, including identifying genetic and sex‐specific differences in brain structure and function, remain understudied. To bridge this gap, we used C57BL/6J and DBA/2J mice, two of the most widely used inbred mouse strains in neuroscience research, to investigate strain and sex‐specific features of the brain connectome in awake animals using magnetic resonance imaging (MRI). By combining resting‐state functional MRI and diffusion MRI, we found that the motor, sensory, limbic, and salience networks exhibit significant differences in both functional and structural domains between C57BL/6J and DBA/2J mice. Further, functional and structural properties of the brain were significantly correlated in both strains. Our results underscore the importance of considering these baseline differences when interpreting brain‐behavior interactions in mouse models of human disorders.