An artistic representation of more than 1000 cells from a brain map, with each neuron a different colour
The Allen Institute
The largest and most comprehensive 3D map of a mammalian brain to date offers an unprecedented insight into how neurons connect and function. The new map, which captures a cubic millimetre of a mouse’s visual cortex, will allow scientists to study brain function in extraordinary detail, potentially revealing crucial insights into how neural activity shapes behaviour, how complex traits like consciousness arise, and even what it means to be human.
“Our behaviours ultimately arise from activity in the brain, and brain tissue shares very similar properties in all mammals,” says team member Forrest Collman at the Allen Institute for Brain Science in Seattle. “This is one reason we believe insights about the mouse cortex can generalise to humans.”
The achievement – something that biologist Francis Crick said in 1979 was “impossible” – took seven years to complete and involved 150 researchers from three institutions. It began with a team recording neural activity from a portion of a mouse’s visual cortex, that was no bigger than a grain of sand, as it watched movies and YouTube clips.
Next, a second group dissected that same brain region, dividing it into layers 1/400th the width of a human hair, and took pictures of each slice. Due to the delicate nature of the structure, the slicing process couldn’t be stopped for long, so the team took shifts. “We spent 12 days and 12 nights sectioning this millimetre cube of tissue into almost 30,000 layers,” says team member Nuno da Costa, also at the Allen Institute.
From there, a third team used AI to trace all the cells and reconstruct each slice into a 3D map. “It was like asking AI to do the world’s hardest colouring book,” says Collman. “You have 100 million images in three dimensions and every single cell has to get coloured with a different crayon. The AI has to decide where one cell starts and the next one stops.”
This data was finally combined with the functional activity recorded at the start of the project so that what the mouse was watching could be linked with the corresponding activity in the brain. The resulting map illustrates the staggering complexity of the brain. Despite its diminutive size, it contained more than 200,000 cells with 4 kilometres of branches between them, and 523 million synapses joining the cells together.
The data is already challenging assumptions about how neurons communicate, revealing that they not only target nearby cells, but actively hunt out other cells dedicated to processing the same visual stimuli.
The researchers hope their map will bridge some of the gaps in knowledge between neural activity and behaviours, eventually helping unravel complex traits like intelligence. “It is ground-breaking work that will be invaluable to the scientific community,” says Nathalie Rochefort at the University of Edinburgh, UK.
Beyond its immediate applications, da Costa says we might even be able to test theories of consciousness. “If someone has a theory of consciousness, they might be able to ask questions of this data, which could then support their theory or reject it.”
The work builds on another study published last year that mapped every neuron in the adult fly brain – a breakthrough that has already revolutionised the field, says Rochefort. For instance, it has helped scientists better understand the circadian rhythms that affect everything from sleep to metabolism.
She says this new map will be invaluable, allowing researchers to make comparisons between it and other maps of different species to examine what cells, wiring principles and functional properties are specific to one species or conserved across several of them, “ultimately shedding light on what makes us human”.
The project is published in a series of eight papers in Nature journals.
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