How the brain reorganizes to form motor memories

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How the brain reorganizes to form motor memories

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When you learn how to ride a bike or play a musical instrument, your bodily movements are uncoordinated at best. But with time and a lot of repetition, the motor neurons in your brain create a kind of shorthand between mind and muscle. The associated movements eventually become so ingrained that jumping on a bike or playing with a scale seems almost automatic.

What are the cellular underpinnings of how this motor learning process works? In a study published this week in neuronAnd the Led research team Dr. Simon Chen from Ottawa College of Medicine It offers valuable new insights into this enduring puzzle of neuroscience.

lab It focuses on uncovering how memories are encoded and stored in the brain, especially with motor learning, the complex process of how our body muscles move and coordinate. with This is the last studyChen’s research team explored the mechanisms involved in regulating motor memory acquisition and consolidation during repetitive practice.

Dr. ChenCanadian Research Chair in Neural Circuits and BehaviorHe says the study findings may be useful in developing therapeutic targets that could help restore motor functions in patients with Parkinson’s disease, stroke or brain injury. This is important because restoring gross motor coordination and recovering lost movements is a very difficult battle for these individuals.

“If we understand how the acquisition of motor skills is regulated in the brain, perhaps one day we can help stroke or Parkinson’s disease patients regain those skills during the rehabilitation process,” he says.

The study focused on mice, not humans. But because scientists believe that the mechanisms of memory formation are very similar in mice and humans, it is likely that the findings are deeply relevant to people.

So how did the experiments work?

By restricting the head movements of mice during the imaging phaseAnd the Which allows scientists to scan the brain with single-cell precision, the team trained the animals to perform a specific motor task: reaching for and grabbing food pellets from an automated delivery rack.

At first, head-chained mice were hesitant and clumsy when grabbing the pellets. The researchers conducted a detailed analysis of the animals’ movements using DeepLabCut, a deep learning software toolkit that combines motion capture videos with artificial intelligence. They found that with repetition and time, the mice formed stereotypical reaching and grasping movements that eventually allowed them to secure food with ease.

The team wanted to see the activation of neurons for these reaching and grasping movements — and to watch the formation of synaptic pathways in the brain as they occur.

“We were able to observe brain changes while the mice were actually learning this task,” says Dr. Chen, assistant professor in the College of Medicine’s Department of Cellular and Molecular Medicine.

Using two-photon imaging, a type of microscopy that allows visualization of living tissue at a micrometer scale, his team was able to watch the reorganization of dendritic spines between excitatory neurons in the primary motor cortex as head-mounted mice performed these granules. – Grab actions over time. Dendritic spines—neural structures at lollipop-like synapses with thin sticks and bubble-like peaks—are key to memory formation and storage.

Zooming in to the cellular level, the researchers discovered that motor learning selectively induces expression of an activity-dependent “transcription factor” called NPAS4 in the primary motor cortex.

What these new findings reveal, says Dr. Chen, is that expression of this transcription factor triggers a learning-related inhibitory neural pool that modulates inhibition in the primary motor cortex. This modulates the reorganization of dendritic spines between excitatory neurons during learning.

NPAS4 primarily regulates genetic changes in inhibitory neurons that control the activity of these neurons similar to how a volume slider controls laptop speakers. These findings “also show that neuronal specific induction of transcription factor acts as a specific feature that underlies the formation of learning-acting neurons,” says Dr. Chen.

In other words, the repetition of movements over time altered the inner workings of the animals’ primary motor cortex – the part of the brain that only mammals have, and which controls complex movements.

The team found that expression of the transcription factor NPAS4 in inhibitory neurons is key to how your brain outperforms choices to form the strongest motor memories of specific movements — and it must be constantly re-expressed for those memories to be cemented and refined. in your mind while doing repetitive exercises.

Reference: Yang J, Serrano P, Yin X, Sun X, Lin Y, Chen SX. Clusters of functionally distinct NPAS4-expressing somatostatin interneurons are important for learning motor skills. neuron. 2022; 0 (0). dui: 10.1016 / j.neuron.2022.08.018

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