Bernstein members involved: Paul Pfeiffer, Susanne Schreiber

Researchers at Humboldt-Universität zu Berlin and Yale University have investigated how mitochondria, the cells’ energy producers, are distributed in the brain. Their findings open up new perspectives on the organisation of neuronal networks.

Mapping the brain is currently experiencing a huge boom. Thanks to artificial intelligence and state-of-the-art electron microscopy, researchers are now able to reconstruct the nerve networks of a wide range of animal species – from insects to humans – in unprecedented detail. This results in complex connectomes, three-dimensional maps that show how thousands of nerve cells are connected to each other.

Cellular fingerprint

However, a study now published in the journal Science by researchers from Humboldt-Universität zu Berlin (HU) and Yale University (USA) looks inside these networks. Instead of just looking at the interconnections between cells, they analysed how the “power plants” of the cell, the mitochondria, are distributed within the neuronal network.

Mitochondria provide energy for almost all processes in the body and fulfil far more tasks than previously assumed: They influence the transmission of signals between nerve cells, control sleep and help decide whether a cell lives or dies. Each nerve cell contains hundreds of these tiny organelles. As the brain consumes a particularly large amount of energy, their arrangement can provide crucial information on the functioning of neuronal circuits.

For their study, the international research team analysed an electron microscopy data set of the fruit fly brain with over 100,000 mitochondria – a volume of data that would have been unthinkable just a few years ago – and developed new statistical methods to identify biological structures from this abundance. One surprising result: the shape of the mitochondria acts like a cellular fingerprint. Based on their external shape alone, the researchers were able to predict which cell type the organelles belong to and which neurotransmitter, i.e. biochemical messenger substances, the respective nerve cell utilises. Their distribution also follows clear rules: Mitochondria cluster near synapses, differ between cell areas and show characteristic distribution patterns depending on the cell class.

In comparison with a mouse connectome, many of these principles proved to be surprisingly similar. However, one detail distinguishes the two species: While mitochondria in fruit flies are spaced apart, in mice they form clusters – an observation that raises new questions about the functional significance of this arrangement.

New insights into the performance of the brain

“When we include mitochondria in the analysis of connectomes, we see the brain from a completely new perspective,” says Susanne Schreiber from Humboldt-Universität who led the study together with Damon Clark from Yale University. “It’s not just about which cells are connected, but also about how each cell organises its interior to enable and best support these connections.”

The study bridges the gap between cell biology and systems neuroscience. It shows that the performance of the brain does not depend solely on its wiring, but also on the microscopic organisation of its energy systems. The analysis illustrates how finely tuned the processes within cells are – a finding that suggests that other organelles in connectomes should also be investigated in future in order to understand their role in the function of neuronal circuits.