New Moves in Neuroscience

According to Carnegie Mellon neuroscientists, there is a clear leader and sidekick when it comes to generating movements.

During purposeful movement, whether reaching for a cookie or walking around your house, two parts of the brain are vital. The motor cortex — located around where sunglasses might sit on top of the head — is connected with the striatum, a region deep on the inside of the brain that is affected by Parkinson's disease. These brain areas are a dynamic duo for controlling movement, yet despite their importance for movement, their relationship with each other was not well understood. One recent study had introduced the idea that despite its name, the motor cortex was not necessary for movement once an action had been learned.

To investigate these questions, Carnegie Mellon neuroscientists removed the motor cortex from the equation. By damaging the motor cortex in a manner similar to a stroke, the researchers could establish what the motor cortex had to offer to the striatum and behavior. In a new paper published in Neuron, Mark Nicholas, a graduate student in the Department of Biological Sciences and first author, and Eric Yttri, Eberly Family Associate Professor of Biological Sciences, found that the striatum was taking all of its cues from the motor cortex when it comes to movement.

"We were looking to answer how the motor cortex and striatum work together," Nicholas said. "How is behavior produced and executed without a motor cortex? Can it be produced or executed without a motor cortex? And how does the striatum work in the absence of a motor cortex?"

To investigate the connections between the motor cortex, the striatum and behavior, Nicholas and Yttri observed mice walking in a T-maze and performing a skilled reaching task by using a small joystick to obtain rewards. Throughout both tasks, the researchers measured the mice's behavior, and during the joystick task, they recorded striatal responses. They then lesioned primary motor cortex and recorded how behavior and striatal activity was affected.

A day after the lesions, Nicholas and Yttri found that there was significantly reduced activity in the striatum in the lesioned mice. Though the striatal activity increased 10 days after the lesions compared to one day after the lesions, activity never returned to pre-lesion levels, and the striatum's activity was significantly altered. The same effects were not observed in the control mice with lesions to other parts of cortex.

The motor cortex lesioned mice had difficulties with the joystick tasks. On the first day after the lesions, the mice were unable to use the joysticks. By day 10, the mice regained enough function to use the joysticks and perform the tasks, but they were only able to do the minimum required for a reward.

The mice displayed altered behavior as well. Though the mice were capable of walking, they would freeze when they encountered a choice where they would have to change their motor state, such as turning at the end of a T-maze. This behavior is similar to clinical freezing of gait (FOG), which occurs during conditions such as Parkinson's disease.

"It's a very striking finding," Nicholas said. "It makes me think that a motor command to do an action has to pass through the primary motor cortex to allow for that initiation of changing of a motor state."

Nicholas and Yttri plan to further investigate the interactions between motor cortex and the striatum to better understand how these parts of the brain work together. Because Yttri investigates regions of the brain related to Parkinson's disease, he said he found the FOG response in the mice was particularly notable.

"This series of experiments gave us some key insights, but it still only gives us a fairly broad perspective," Yttri said. "We will be following up with more in-depth studies of the freezing of gait effects and the communication between these areas. The goal is to get down in the finer details, to better establish the connections of elements of the circuit."

Nicholas and Yttri's publication is entitled "Motor Cortex Is Responsible for Motoric Dynamics in Striatum and the Execution of Both Skilled and Unskilled Actions." The work was funded by the Charles E. Kaufman Foundation, the Pittsburgh Foundation, the Whitehall Foundation and the Brain Research Foundation.