Helen M. Kamens¹, Tanzil M. Arefin^2,3,4,5,6, Hayreddin Said Unsal^3,7, Thomas Neuberger^2,3, Nanyin Zhang^2,3,4

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 potentially predispose animals to different responses. Over the past decade, tremendous effort has been made in mapping 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 fMRI 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 the brain-behavior interactions in mouse models of human disorders.

¹Department of Biobehavioral Health, The Pennsylvania State University, University Park, USA

²Huck Institutes of Life Science, The Pennsylvania State University, University Park, PA, USA.

³Department of Biomedical Engineering, The Pennsylvania State University, University Park, USA.

⁴Center for Neurotechnology in Mental Health Research, The Pennsylvania State University, University Park, USA.

⁵Department of Neuroscience, University of Rochester Medical Center, Rochester, New York, USA

⁶Center for Advanced Brain Imaging and Neurophysiology, University of Rochester Medical Center, Rochester, New York, USA

⁷Department of Electrical and Electronics Engineering, Abdullah Gul University, Kayseri, Türkiye

Acknowledgments

This work was supported by the National Institute on Drug Abuse (DA060335, H.M.K.), Penn State’s Department of Biobehavioral Health, Social Science Research Institute, and Consortium on Substance Use and Addiction. The authors would like to acknowledge the Huck Institutes High Field Magnetic Resonance Imaging Core Facility (RRID:SCR_024461) for use of their Bruker Biospec 70/30.