Potential insight into mobility disorders such as Parkinson’s and more

Among the numerous marvels of the brain is its capacity to refine movements through repetition — whether it’s a dance routine, piano piece, or tying shoelaces.

For many years, neuroscientists have recognized that these actions necessitate a collection of brain regions referred to as the basal ganglia.

A recent investigation in Nature Neuroscience, conducted by researchers from Harvard, revealed that this so-called “learning machine” communicates using two distinct codes — one for newly acquired movements and another for instinctive “natural” actions.

These unexpected discoveries with laboratory animals might illuminate human motor disorders like Parkinson’s disease.

“Upon comparing the codes across these two behavioral categories, we noted significant differences,” stated Bence Ölveczky, a professor of organismal and evolutionary biology (OEB). “They were entirely unrelated. Each code accurately portrayed the animal’s actions, yet the linguistic structure was markedly different.”

Situated in the midbrain beneath the cerebral cortex, the basal ganglia are engaged in reward processing, emotions, and motor regulation. This area also represents the origin of several troubling movement disorders: Huntington’s disease, Tourette’s syndrome, and Parkinson’s emerge from various abnormalities in the basal ganglia.

While it has long been established that the basal ganglia are vital for motor regulation among mammals, it remains ambiguous whether this brain region governs all types of movements or solely those for specific tasks.

Some scholars suggest that the basal ganglia serve as a center for movements learned through practice, but not for other habitual actions. Others propose it contributes to all movements.

To clarify this enigma, the researchers investigated a specific section of the basal ganglia in rats — the dorsolateral striatum (DLS), which is connected to learned behaviors.

The team observed rats during two separate activities: free exploration and a trained task where they learned to press a lever twice within a designated time frame to receive a reward. To monitor their movements, the researchers utilized a setup of six cameras positioned around the enclosure along with software designed to categorize behaviors.

In previous studies, the team excised the DLS from rats, who afterward displayed no differences during free exploration, indicating that it played no role in instinctive behaviors like ambulating or grooming.

However, the same rats were critically hindered when attempting learned tasks, demonstrating that the DLS was crucial for newly acquired skills.

“There was a dramatic shift, akin to night and day,” remarked Kiah Hardcastle, a postdoctoral researcher in the Ölveczky lab and primary author of the recent study. “The animal could perform a task remarkably well, executing a standard movement repeatedly, nearly 30,000 times. Then you injure the DLS, and they cease to perform that action altogether.”

In the recent study, the researchers aimed to comprehend the neural activity during these behaviors by implanting minute electrodes into the brains of rats and recording the electrical activity of neurons while they engaged in both free exploration and the learned task.

Unexpectedly, they found that the basal ganglia employed two distinct “kinematic codes” — or patterns of neuronal electrical activity — during the learned task and natural actions.

“It seems that the basal ganglia ‘speak’ different languages when the animal engages in learned as opposed to instinctive movements,” expressed Ölveczky. “Areas of the brain downstream that regulate movement are familiar only with one of these languages — the one used during learned behaviors.”

In their paper, the researchers concluded that the basal ganglia switch between being a key participant and a mere observer.

Hardcastle speculated that the basal ganglia might struggle to entirely halt electrical signaling when not directing behavior, resulting in a harmless “null code.”

Ölveczky noted that these findings could be applicable to humans, given that the structures beneath the cerebral cortex are believed to have remained significantly unchanged throughout evolutionary history. He believes this study highlights the fundamental roles the basal ganglia play in learned actions — but not necessarily in habitual motor control.

Furthermore, he posits that the findings provide insights into potential failures occurring in certain human movement disorders.

“Our research suggests that the pathology linked with Parkinson’s can be interpreted as the impaired basal ganglia communicating nonsensically, yet in an extremely loud and forceful manner,” stated Ölveczky. “Consequently, it interferes, in a meaningless way, with behaviors it would not typically govern.”

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Federal financial support for the research was provided by the National Institutes of Health.