Specific brain cells rewire to control motor movement timing

Whether speaking, driving, or playing an instrument, nearly everything we do requires precise control over the timing of our actions. When we learn new skills, we must learn not only what movements to make but how to time them precisely. Scientists at MPFI have now identified the specific brain cells that are reshaped to learn movement timing. While nearly all brain cells can rewire, this research shows that they are not redundant. Rather, they play specific roles in shaping the brain during learning.

A novel approach

Understanding which neurons rewire and what role they play in learning was the primary motivation for MPFI scientists Shouvik Majumder and Hidehiko Inagaki, who led the study recently published in Nature Communications. However, traditional ways of studying learning did not provide this information.

We had good knowledge of how brain activity changes during learning to shape movement timing, but to really understand how the brain learns we needed a way to test how the rewiring of specific neurons changes brain activity and behavior,"

Shouvik Majumder, MPFI scientist

The team set out to answer this central question by studying mice as they learned to change the timing of their movements. They trained mice to wait increasingly longer durations after a tone before retrieving a reward. While the mouse learned, the scientists recorded the electrical activity of thousands of neurons in the premotor cortex, an area of the brain responsible for movement timing. They found that as the mouse learns to delay movement, the patterns of brain activity in this region shift.

But the key question was whether rewiring in certain neurons was driving these changes. And if so, did every neuron shape these patterns the same way, or did different neurons play different roles?

To answer these questions, the scientists used tools to shut down rewiring machinery in specific neurons during learning. At the same time, they recorded activity patterns in this region and monitored the mouse's behavior. This approach allowed them to link rewiring in specific cell types to the shifts in the brain's activity patterns that mediate learning, a connection that had previously been difficult to establish directly.

Key finding

While synaptic rewiring is possible in all cell types, the team found it wasn't interchangeable. Blocking the rewiring machinery in one neuron class, called pyramidal tract (PT) neurons, stopped learning entirely, while blocking it in another more abundant type, called intratelencephalic (IT) neurons, didn't. Additionally, rewiring in two distinct subgroups of PT neurons played complementary roles in adjusting the motor timing during learning.

Senior author Hidehiko Inagaki explains, "We discovered that while plasticity in the brain is widespread, it is not redundant. Plasticity in specific cell types plays precise roles that are required to shape neural activity and lead to changes in behavior."

The team is now applying this approach to study other aspects of motor learning. They hope that their work offers a template for other scientists studying learning, helping explain how rewiring in specific cell types coordinates diverse types of learning. With further research, scientists may be able to pinpoint deficits to specific neuronal cell types.