Reaching, grasping, and object manipulation are key components to the lives of mammals with prehensile forelimbs. Although the movements happen automatically, the complexity of the limb creates a challenge for the nervous system and, more specifically, the motor cortex which is receiving sensory information and other kinds of feedback.

Although it has been shown that the motor cortex controls the arm by sending neural activity patterns to the spinal cord and brainstem, how these patterns are generated has remained unclear.

New research in mice, published recently in Nature in a paper titled “Cortical pattern generation during dexterous movement is input-driven,” looked into the role of the feedback signals entering the motor cortex, untangling how and when they’re necessary to guide dexterous movements like grasping.

 

Using high-speed video cameras, researchers tracked mice’s arm motions as the animals reached out and grasped a food pellet. Then, they tested how switching off different parts of the brain affected this dexterous movement [Sauerbrei et al./Nature 2019]

“What we show is the motor cortex is fundamentally different from that,” said Britton Sauerbrei, PhD, a postdoctoral associate at the Howard Hughes Medical Institute’s Janelia Research Campus. “You can’t just give the cortex a little kick and have it take off and generate that pattern on its own.” Instead, the motor cortex needs to receive feedback throughout the entire movement.

He and his colleagues trained mice to reach for and grasp a food pellet, a behavior that depends on the motor cortex. In some animals, they turned off the thalamus, a switchboard in the brain that directs sensory information and other kinds of feedback to and from the cortex.

When the researchers blocked the signals coming into the motor cortex before the mice began to reach, the animals didn’t initiate movement. And when incoming signals were blocked mid-reach, mice stopped moving their paw closer to the pellet.

The authors wrote that “perturbing cortex to an aberrant state prevented movement initiation, but after the perturbation was released, cortex either bypassed the normal initial state and immediately generated the pattern that controls reaching or failed to generate this pattern. The difference in these two outcomes was probably a result of external inputs.”

The rhythm of those signals also matters, the researchers showed. In another experiment, they stimulated neurons carrying signals from the thalamus to the cortex with different patterns of incoming signals. The frequency of the stimulation affected the motor cortex output, with fast pulses disrupting mice’s grasping skills.

Using simultaneous recordings, the team found that “both thalamic activity and the current state of cortex predicted changes in cortical activity. Thus, the pattern generator for dexterous arm movement is distributed across multiple, strongly interacting brain regions.”

The signals entering the motor cortex via the thalamus come from all over, and it’s not yet clear which ones are most important for directing movement, said Adam Hantman, PhD, a group leader at Janelia and the paper’s senior author. Inputs to the thalamus include sensory information about the position of the arm, visual information, motor commands from other brain regions, and predictions about the upcoming movement. Using tools developed by the Janelia project team Thalamoseq, Hantman’s lab plans to switch specific regions of the thalamus on and off to test which inputs are really driving the behavior.

For Hantman, the complexity of understanding these kinds of motor skills is what makes studying them so exciting. “If you want to understand a behavior, and you think you’re going to study one region, you might be in a tough position,” he said. “You need to understand the whole central nervous system.”

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