In a laboratory, a mouse grips a toy-like steering wheel, eyes fixed on a flickering circle on a screen. A flick of its paws brings the circle to the centre and a reward of sweetened water follows.
This small act of dexterity has now helped scientists produce something far grander: the first brain-wide map of how a mammal makes a decision.
In two papers the International Brain Laboratory, a consortium of 22 research groups from Europe and America, charted how activity ripples across the brain as a decision takes shape.
The project’s scope is staggering: more than 600,000 neurons were recorded across 279 brain regions.
The implications extend beyond mice. Human brains, though far larger and more complex, share a similar architecture. Understanding how decisions emerge from the distributed chatter of cells could eventually illuminate disorders where this chatter goes awry, such as schizophrenia or Parkinson’s.
Until now, studies of decision-making have focused on small clusters of cells within single regions of the brain. The study, published in Nature, shows how limiting that approach has been.
A decision, it turns out, is not hatched in a single cortical enclave, but emerges from a grand orchestration of regions spread across the brain, including those once understood to be the preserve of movement rather than thought.
At first the mouse’s brain is relatively silent. As the circle appears on the screen, visual areas at the back of the brain stir into action.
Activity swells across several regions as the animal accumulates evidence about what it sees. As a choice crystallises, areas linked to movement ignite and the mouse pushes the wheel to play its computer game. When the sugar water reward arrives, the whole brain lights up in a final surge of activity.
What is most striking, according to researchers, is how the activity is spread out. “Decision-making is indeed very broadly distributed throughout the brain, including in regions that we formerly thought were not involved,” said Ilana Witten, a professor at the Princeton Neuroscience Institute and one of the project’s leaders. This brainwide activity means that neuroscientists will need a broader approach when studying complex behaviour.
The results also suggest that expectations shaped by recent experience are stored all over the brain, not just in one spot. Surprisingly, these expectations are not only found in areas associated with thought, but also areas of the brain that process sensory information and control movement.
Each of the 22 laboratories was assigned a portion of the brain to monitor with high-density electrodes and the scale of collaboration marks its own breakthrough.
Professor Tom Mrsic-Flogel, of the Sainsbury Wellcome Centre at University College London and a core member of the consortium, said: “We’d seen how successful largescale collaborations in physics had been at tackling questions no single lab could answer, and we wanted to try that same approach in neuroscience. The brain is the most complex structure we know of in the universe; understanding how it drives behaviour requires international collaboration on a scale that matches that complexity.”
The mice’s task was, by contrast, fairly simple. They sat before a screen where circles flashed left or right. By twiddling the wheel, they could pull the circle to the centre and win a sip of sugar water. Sometimes the circle was faint, forcing the animals to rely on memory and expectation — a way of testing how recent experience influences decision-making.
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