A triple-network organization for the mouse brain.

Area of Science:

• Neuroscience
• Comparative Neuroanatomy
• Psychiatric Research

Background:

• The triple-network model explains brain disorder phenotypes through interactions between salience, default-mode, and central executive networks.
• While homologous networks exist in animal models, their integration into a unified triple-network organization remains unclear.

Purpose of the Study:

• To investigate the conservation of the triple-network organization across species (human, macaque, mouse).
• To validate the triple-network model in a mouse model of depression.
• To refine the anatomical model of these networks and explore their cross-species comparability.

Main Methods:

• Analysis of resting-state fMRI datasets from humans, macaques, and mice.
• Development of a data-driven method to map mouse brain coordinates to human standards.
• Utilizing viral tracers, optogenetics in mice, and human tractography for anatomical and functional validation.
• Testing model predictions in a mouse model of depression.

Main Results:

• Demonstrated conserved spatio-temporal properties of triple-network elements across human, macaque, and mouse brains.
• Validated the triple-network model's applicability in a mouse model of depression.
• Identified serotonin's involvement in the salience network, contrary to expectations.
• Developed a method for humanizing mouse brain networks for trans-species comparison.

Conclusions:

• The triple-network system is conserved in mice, sharing properties with humans, including in disease contexts.
• The findings support a unified triple-network framework for understanding brain function and disorders across species.
• The developed methods facilitate data-driven, trans-species comparisons of brain networks.