The University of Minnesota Medical School received a $16 million grant from the National Institutes of Health (NIH) Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative to support the project of unraveling the mysteries of the brain’s ‘wiring diagram.’ Using advanced techniques, this research seeks to discover how the brain’s neurons are connected and communicate with each other.

The project aims to better understand how complex neural pathways generate human behaviors. The focus is mapping connections between specific brain regions responsible for higher-level functions like attention and decision-making. Traditional methods for this kind of mapping have limitations, so the team will combine advanced techniques to bridge the gap.

BRAIN CONNECTS follows in the footsteps of the Human Connectome Project. However, we’re taking it further by using advanced MRI together with other emerging tools that rely on optical imaging and cell labeling techniques. This approach will provide us with a more detailed and much clearer picture of the brain’s circuits,” explained contact principal investigator Kamil Ugurbil, PhD.

“Current techniques lack either the resolution or the ability to scale across and map out large regions of the entire brain, information that is essential for unraveling the mysteries of this incredible organ,” added John Ngai, PhD, director of the NIH BRAIN Initiative. “Following years of careful planning and input from the scientific community, BRAIN CONNECTS, which represents our third, large-scale transformative project, aims to develop the tools needed to obtain brain-wide connectivity maps at unprecedented levels of detail and scale.”

Important investment

“The NIH is making an important investment in uncovering one of the most important features of brain anatomy—its wiring diagram, or how neurons are set up to talk to each other. In future years, this will pay major dividends in terms of neuromodulatory treatments of brain disorders,” noted Sarah Heilbronner, PhD, principal investigator and associate professor at Baylor College of Medicine.

Their goal is to create accurate wiring diagrams using a multi-modal, cross-species, multi-scale approach. This will provide crucial insights into brain connectivity and its impact on cognition, behavior, and disease.

“Mapping the animal model brain’s wiring has been a challenging goal, but recent advances in high-resolution MRI and microscopy are opening doors to uncovering its intricate architecture. This knowledge will shape generations to come,” said Jan Zimmermann, PhD, principal investigator and associate professor at the U of M Medical School.

The team of scientists involved in this project includes researchers from the U of M College of Science and Engineering; University of Nottingham; Shenzhen Institute of Advanced Technology; University of Texas Austin; Oxford University; Vanderbilt University; Cold Spring Harbor Laboratories; and the Allen Institute.

For the next steps, the team will focus on advancing treatments for brain disorders. Numerous psychiatric and neurological conditions involve disrupted brain connectivity. Understanding and addressing this connectivity issue is an essential step to implementing effective solutions.

This grant leverages the knowledge and resources in advanced microscopy through the University of Minnesota’s Medical Discovery Team (MDT) on Optical Imaging and Brain Science.

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