The Role of Motor Cortex in Striatal Motor Dynamics and Execution of Skilled and Unskilled Actions

Neurology Basic Medical Sciences Life Sciences Medicine Cell Biology
motor cortex striatal dynamics action execution neuroscience lesions

Exploring the Crucial Role of the Motor Cortex in Basal Ganglia and Dynamic Motor Control

Research Background and Motivation

The role of the motor cortex (Motor Cortex, M1) in motor generation and regulation has long been a significant topic in neuroscience. The interaction between M1 and the striatum in selecting and executing goal-directed actions is crucial. However, how exactly these functions are coordinated remains unclear. There is a debate about whether the motor cortex is the sole origin of motor commands or whether it only plays a role in motor regulation. In recent years, some studies have suggested that the basal ganglia might be the core area for selecting and executing actions rather than M1. Other research shows that M1 damage does not significantly affect some simple motor tasks, further deepening the divide in understanding M1 functions. To clarify the exact role of the motor cortex in motor generation, Nicholas and Yttri’s team (2024) conducted bilateral lesions in the M1 of mice and recorded their striatum activity and motor performance, aiming to reveal whether the motor cortex is crucial for generating and regulating different types of movements.

Source and Publication Status

This paper, authored by Mark A. Nicholas and Eric A. Yttri from the Department of Biological Sciences at Carnegie Mellon University, was published in the October 23, 2024 issue of Neuron (Volume 112, Pages 3486–3501). This work is © by Elsevier, covering rights related to text and data mining, AI training, etc.

Research Design and Methods

The study utilized a bilateral M1 lesion mouse model to observe changes in motor performance and striatum activity. The subjects were experimental mice trained to complete two types of motor tasks (self-paced and cued tasks). The M1 lesion was induced using the aspiration method, cutting off all M1 inputs to the striatum and simulating effects closer to neurodegenerative lesions. By monitoring behavior and neural activity daily, the research team precisely recorded the immediate effects of the lesions and performed a multidimensional in-depth analysis of behavioral and neural recovery trajectories post-lesion.

Experiment Procedure

  1. Mouse Motor Task Training: Initially, the experimental mice were trained to complete self-paced and light-cued motor tasks. These tasks required mice to perform specific directional reaching actions on a joystick to obtain rewards. During task execution, the researchers recorded neuronal activity in the striatum.

  2. Establishment of Lesion Model: Bilateral aspiration lesions were performed in the M1 area to sever all M1 projections to the striatum. Immediately post-lesion, neurological behavior monitoring observed the direct impact on behavior and striatum activity.

  3. Behavioral and Neural Activity Data Collection: The research team recorded the motor performance and striatum neuronal activity of the mice daily, focusing on differences across various periods pre-and post-lesion. Rich data analysis methods were used, including striatum unit activity analyses and time-dynamic decoding of behavior trajectories.

Research Results

  1. Significant Drop in Motor Performance: In the days following M1 lesions, mice exhibited severe motor impairments, with a sharp decline in their ability to perform reaching tasks. In the first week post-lesion, the number of effective reaches significantly decreased, from an average of 9.0 reaches per minute to 0.23. While behavior gradually recovered about 10 days post-lesion, it did not reach pre-lesion levels, and motor trajectories still showed significant deformation and irregularity.

  2. Loss of Striatum Neuronal Activity: The lesions resulted in the loss of activity in striatum motor-related neurons (SPNs and FSIs). Before the lesions, 82% of SPNs exhibited significant motor-related activity, but post-lesion, this figure dropped dramatically, with less than 10% of SPNs maintaining motor-related activity by the second day. Moreover, the lesion erased SPNs’ modulation characteristics for movement amplitude, and even as behavior recovered later, neuronal activity did not regain its pre-lesion kinematic features.

  3. Gait Freezing in Spontaneous Behavior: In an untrained T-maze experiment, mice could perform basic walking actions but exhibited severe “gait freezing” when needing to change direction at intersections. Mice paused for extended periods at intersections (up to 68.89 seconds), persisting in mid-step rather than stopping or grooming, a phenomenon akin to clinical ‘Freezing of Gait’ (FOG) symptoms.

  4. Loss of Striatum Dynamic Decoding Ability: Decoding experiments revealed that pre-lesion striatum activity could reliably predict the real-time position of the mice’s joystick (average mean square error of 0.018). However, this ability completely vanished post-M1 lesion, indicating that the striatum alone struggles to generate motor commands.

  5. Insignificant Impact on Non-Target Cortex: As a control group, a similar lesion was performed on the parietal cortex (PPC) of another mouse group. Results showed no significant impact on behavior performance and striatum neuronal activity, supporting the notion that M1 plays a more central role in motor generation.

Conclusion

This study demonstrates that M1 has an irreplaceable role in selecting and generating goal-directed movements. Lesion-induced motor impairments and dynamic striatum losses further corroborate this point. Although behavior gradually recovers 10 days post-lesion, this recovery is due to compensatory mechanisms in other brain regions and does not restore the original neural dynamics. The motor control function of the striatum relies on movement commands provided by M1 rather than independently generating motion. In the absence of M1, striatum activity alone is insufficient to maintain complete goal-directed motor performance. Additionally, M1’s role in gait regulation resembles the neural basis for human FOG symptoms, providing potential targets for neurological stimulation in clinical treatments.

Scientific Significance and Application Value

Through meticulous experimental design and high-density data collection, this study deeply reveals the motor cortex’s central role in motor generation and dynamic regulation, especially its dominant influence on striatum activity. The findings provide a new perspective for understanding the hierarchical relationship between the motor cortex and basal ganglia in motor control and deliver direct evidence for the neurological mechanisms of motor disorders like freezing of gait, with significant clinical reference value. Moreover, for the first time, the study details the dynamic changes in the striatum post-motor cortex lesion, offering a new direction for future research into compensatory mechanisms in motor disorders.