A mouse brain holds around 70 million neurons, yet a team from UC San Diego has demonstrated that waking up roughly 20 of them can be enough to launch a skill the animal has practised.
The study, published in Nature, tackles a long-running puzzle. When we learn a movement, whether swinging a racket or running through scales on a keyboard, a recognisable pattern of activity appears in the motor cortex. Scientists have debated whether that pattern actually drives the action or merely reflects instructions coming from elsewhere in the brain.
To test it, the team spent two weeks teaching mice a simple routine: when a tone sounded, press a little lever and hold it down for a full second, with water as the reward. They then watched the animals’ cortex through a two-photon microscope while the cells, engineered to glow when active, lit up. Across 14 mice they followed close to 15,000 neurons. Using another laser beam shaped into holographic patterns, they could then fire hand-picked neurons individually.
Stimulating about 20 neurons that normally fire just before a lever press caused the whole learned pattern to ripple outward, and the animal frequently went on to carry out the movement. Cells that become active only after a movement starts did a poorer job, and the effect depended on whether the animal was engaged in the task.
Senior author Takaki Komiyama called it “surprising” that nudging so few cells could steer both widespread activity across the cortex and the animal’s actions. The experiments were led by doctoral researcher Qiyu Chen and build on groundwork laid by the late An Wu, a member of the lab killed in a 2023 blaze in Montreal.
The researchers hope the insight could one day inform therapies for stroke or paralysis, although moving from mouse to human remains a long road.
