Fueling the mind: New map reveals where the brain gets its energy

Every thought we have, every emotion we feel, and every memory we hold requires one essential ingredient: energy.

This energy is produced by mitochondria – tiny, bean-shaped structures inside our cells that act like batteries, powering everything our body does.

In the brain, mitochondria are especially important. But for all their importance, we still know very little about how these microscopic engines are distributed throughout the brain, how they vary, or how they impact mental health.

Map of mitochondria in the brain

To investigate, scientists at Columbia University created a tool called MitoBrainMap, the first comprehensive map of mitochondria distribution across the human brain.

This tool offers a closer look at how energy is managed in different parts of the brain, and what that means for our mood, memory, and overall brain function.

The study was led by Martin Picard, associate professor of behavioral medicine at the Robert N. Butler Columbia Aging Center, along with with Michel Thiebaut de Schotten, who is a research director at the University of Bordeaux.

“There’s an emerging notion that energy is really important to health, but we don’t have a way to look at bioenergetics across the entire human brain,” explained Picard.

“MitoBrainMap marks a milestone toward understanding the energy landscape underlying brain health, with implications for tracing the origin of neurodegenerative and neuropsychiatric disorders and developing new approaches to treatment.”

Detailed energy profile of the brain

Studying mitochondria in the brain isn’t easy. Traditional brain scans like MRIs give a big-picture view, while microscopic studies only focus on individual cells. The researchers needed a way to connect these two scales.

They started with a frozen human brain. From this brain, they sliced out a section and cut it into 703 small cubes, each measuring just 3 millimeters on each side. That’s about the size of a grain of sand and similar to the resolution of standard brain scans.

Inside each cube, the experts measured two things: the number of mitochondria and how efficiently those mitochondria could convert nutrients into usable energy.

These results were then used to build a detailed energy profile of that single brain slice.

Since analyzing all 50,000 sections of a whole brain would take years, the team used computational modeling to estimate the energy map for the rest of the brain.

This approach allowed them to create a first-of-its-kind model of how energy is spread out in the human brain.

Mitochondria vary by brain region

The results were surprising. Mitochondria, it turns out, are not uniformly distributed. Their density and energy-producing capabilities vary not just by the type of brain cell, but also by brain region.

Anna Monzel is a computational research scientist who was involved with the single cell mitochondrial phenotyping (“mitotyping”) component of the study.

“These differences are remarkable since all mitochondria originate from the same ‘mother’ pool of mitochondria in the oocyte,” said Monzel.

“But during development they specialize in a cell type-dependent manner to subserve bioenergetic demands and guide the acquisition of specific cellular phenotypes.”

Newer parts of the human brain – those that evolved more recently and help define what makes us human – had more mitochondria.

These mitochondria were also more efficient. That makes sense, considering these newer regions are more energy-hungry than older parts of the brain.

Brain energy and mental function

The team’s initial map is just the beginning. Future work will focus on validating and expanding these findings.

“If validated, our model could be used to estimate the functional properties of mitochondria in the live brain using standard MRI scans, essentially creating the first non-invasive way of peering into the biology of mitochondrial bioenergetics in the human brain,” said study first author Eugene Mosharov, a research scientist in the Department of Psychiatry.

This would open up entirely new ways to study the connection between brain energy and mental function in real time – during learning, emotional experiences, or even illness.

Improving the accuracy of the brain map

The researchers are already working on a second version of MitoBrainMap. They’re analyzing brain samples from 500 individuals, and looking at nine different regions to see how mitochondrial patterns vary from person to person.

These efforts will improve the accuracy of the map and help explain how energy differences might relate to conditions like Alzheimer’s or depression.

“Energy is the missing dimension of biomedicine,” said Picard. “If you think of health as energy, it inspires you to ask different questions. How much energy does it cost to heal the brain? Does the food you eat influence your mitochondria? Do energy constraints affect normal brain function, or the development of Alzheimer’s disease?”

“This MitoBrainMap v1.0 is a step toward understanding the energetics of the brain and the experiences it allows us to have.”

Significance of energy in the brain

By visualizing how energy is distributed in the brain, MitoBrainMap encourages us to think differently about mental health and disease.

It suggests that energy – something we rarely consider – may be just as important as anatomy or chemistry for brain function.

This first version is just a starting point. As scientists continue to build on this map, it could become a powerful tool in understanding not just the brain, but the experience of being human.

The full study was published in the journal Nature.

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