Simons Foundation Launches Collaboration To Uncover How Energy Shapes Brain Computation

The human brain carries out more complex processes than any other organ, and to do this, it needs a lot of energy — roughly 20 percent of what the body generates. However, we still don’t fully understand how the brain creates energy, rations it out or uses its available supply to execute critical functions.

The Simons Collaboration on Brain Energetics (SCOBE), launched today, will explore these questions and how the brain creates and uses energy, as well as how it functions under metabolic stress. The collaboration provides $80 million over 10 years to a group of 26 investigators across systems and computational neuroscience, cellular and molecular biology, engineering and theory.

“Every thought and action depends on neurons performing computations that are extraordinarily costly in energy terms, yet we don’t understand how those energetic limits shape the way the brain is built and how it computes,” says Kelsey Martin, executive vice president of the foundation’s Autism & Neuroscience division. “This collaboration brings together experiments across species and scales with theory to reveal the principles linking energy supply and demand to how neural circuits compute and how behavior arises.”

“The Simons Foundation’s neuroscience collaborations are designed to understand fundamental principles of brain function, and brain energetics is a critical example of that,” says Alyssa Picchini Schaffer, vice president and senior scientific officer of the foundation’s neuroscience collaborations. “Brain energetics likely impacts everything from how the brain carries out computations to our basic understanding of autism, neurodevelopment and aging. It’s one of the backbone constraints for understanding the brain that we need to address to push the field forward.”

SCOBE will focus on four major topic areas:

• Brain energetics at the single-cell level will examine how much energy different types of brain cells need to perform specific tasks (such as firing signals or clearing waste) and how they work together to allocate resources. Researchers also plan to develop new sensors that can track energy-related molecules such as glucose and adenosine triphosphate (ATP) as they move through cells, providing a detailed map of energy allocation and expenditure.
• Energetics across brain circuits will explore how energy availability shapes computational processes (such as vision, navigation and memory) that require large networks of cells. These studies will ask whether more demanding computations require more energy and how the brain prioritizes them when energy is limited.
• Neurovascular coupling will look at the relationship between the brain and its blood supply. These projects will study how neurons interact with blood vessels to change how much energy they receive. Clarifying this process could help scientists interpret findings from techniques like fMRI, which measures changes in blood flow as a proxy for neural activity and which is widely used in current neuroscience research.
• Adaptation to energy scarcity will investigate how the brain adapts to changes in energy availability. The amount of energy shuttled to the brain can fluctuate for many reasons, such as chronic metabolic conditions (like diabetes), decreased oxygen levels or pregnancy. These studies will explore how the brain remains resilient in low-energy environments and what happens when those protections break down.

To address these areas, SCOBE Investigators will study worms, flies, mice and humans. This diversity will also allow them to determine which principles of brain energetics are shared across species.

Like all the foundation’s neuroscience collaborations, SCOBE will have a strong focus on theory, computation and data sharing.

“Not a lot of past research into brain energetics has taken a theoretical or computational approach, so I’m optimistic about what we will learn by applying advanced modeling techniques to integrate diverse data types,” says Hannah Bayer, a senior scientific officer in neuroscience collaborations. “We are also committed to open data and are looking forward to sharing our findings with the broader research community.”

The following are the team of SCOBE Investigators:

Anton Arkhipov
Allen Institute

Ghazaleh Ashrafi
Washington University

Erin Barnhart
Columbia University

Kwabena Boahen
Stanford University

Thomas Clandinin
Stanford University

Daniel Colón-Ramos
Yale University

Emily Jane Dennis
Janelia Research Campus
Howard Hughes Medical Institute

Anna Devor
Boston University

Gaute Einevoll
University of Oslo

Surya Ganguli
Stanford University

Lisa Giocomo
Stanford University

Chenghua Gu
Harvard University

Balijit Khakh
Cardiff University

Laura Lewis
Massachusetts Institute of Technology

Jonathan Polimeni
Harvard University
Massachusetts General Hospital
Stanford University

Priya Rajasethupathy
Rockefeller University

Vidhya Rangaraju
Max Planck Florida Institute for Neuroscience

Nathalie Rochefort
University of Edinburgh

Tim Ryan
Weill Cornell Medicine

Sava Sakadzic
Harvard University
Massachusetts General Hospital

Nirao Shah
Stanford University

Longzhi Tan
Stanford University

Alison Tebo
Janelia Research Campus
Howard Hughes Medical Institute

John Vaughen
University of California, San Francisco

Tim Vogels
Institute of Science and Technology Austria

Gary Yellen
Harvard University