The central nervous system’s primary role is to coordinate movement. Skilled actions depend on multiple processes—planning, initiation, execution, and refinement—and new experiments at the Howard Hughes Medical Institute’s Janelia Research Campus show that the sensorimotor cortex is essential for initiating and carrying out a complex learned movement. When researchers temporarily switched off this cortical region in mice, the animals abruptly stopped mid-task and resumed the exact action as soon as normal cortical activity returned.
Until now, it has been unclear whether the motor cortex acts as the brain’s main commander for voluntary actions or primarily fine-tunes complex movements. In a study led by Janelia group leader Adam Hantman and published in eLife, researchers demonstrate that activity in the motor cortex is critical for producing a learned motor skill.
Neurons in motor cortex become active as animals plan and perform movements, but the precise role of that activity has been debated. Artificial stimulation of cortex can evoke complex motions, yet earlier work found that mice with permanent motor cortex lesions can still complete a trained sequence, albeit with reduced dexterity—swinging a limb more broadly instead of precisely guiding the paw to a target.
To clarify the cortex’s contribution, Hantman and colleagues used optogenetics, a method that gives precise temporal control over specific neurons by expressing light-sensitive proteins and activating them with laser pulses. This approach allowed the team to inhibit motor cortex activity at chosen moments while mice performed a task, and because the inhibition was reversible and brief, it avoided long-term compensation that can confound lesion studies.
Senior scientist Jian-Zhong (Jay) Guo trained mice to reach for a food pellet, grasp it, and bring it to the mouth. During these trained reaches, the researchers applied a laser to activate inhibitory neurons in the motor cortex region controlling the reaching limb. Those inhibitory neurons transiently silenced nearby excitatory neurons, effectively turning the cortex off for the duration of the light pulse.
The behavioral effect was striking. Whenever the laser was switched on after a mouse had begun a reach with its right paw, the animal’s movement stopped immediately—the paw could not progress toward the pellet while the left motor cortex was silenced. “It was as if we had achieved a remote control of the mouse,” Hantman recalls. In some trials, the scientists inhibited cortex after the mouse had secured the pellet; the animal would hold the pellet but be unable to lift the stalled limb to its mouth, sometimes using the opposite paw (controlled by the intact hemisphere) to compensate.
To measure behavior precisely, Hantman’s team recorded each trial and applied machine learning tracking algorithms developed by Janelia group leader Kristin Branson and colleagues. Automated analysis let them test cortical inhibition across many conditions. The pause effect was specific: untrained, routine behaviors like grooming or licking continued uninterrupted during cortical inhibition, indicating that freezing was tied to a learned, goal-directed, complex reach rather than all forelimb movement.
Equally remarkable was how mice behaved when cortical activity returned. In the food-grabbing task, animals resumed the interrupted reach immediately after the laser was turned off, often completing the sequence exactly where it had been paused. In some cases a hungry, trained mouse would initiate the full reach just after release from inhibition even when no pellet was present and no external cue had been given. The mere pattern of inhibition followed by release seemed sufficient to evoke the learned sequence.
These observations led the team to propose that motor cortex activity encodes more than moment-by-moment kinematics; it may also specify a learned endpoint or goal location for the action. The rebound reaches—evoked only in trained, motivated animals—suggest the existence of a motivation-gated motor engram that can be activated by the end of inhibition and then expressed as an intact prehension sequence.
Hantman and colleagues are pursuing how motor cortex stores and represents the intended movement target. “Some of the dynamics revealed by our perturbations provide valuable entry points to uncover the cortical mechanisms that support skilled action,” Hantman says.
Source: Jim Keeley – HHMI
Image Source: Image adapted from the HHMI press release
Original Research: Full open access research “Cortex commands the performance of skilled movement” by Jian‑Zhong Guo, Austin R. Graves, Wendy W. Guo, Jihong Zheng, Allen Lee, Juan Rodríguez‑González, Nuo Li, John J. Macklin, James W. Phillips, Brett D. Mensh, Kristin Branson, and Adam W. Hantman in eLife. Published online December 2, 2015. doi:10.7554/eLife.10774
Abstract
Cortex commands the performance of skilled movement
Mammalian cerebral cortex is known to be critical for voluntary motor control, but precisely which functions depend on cortex remains unclear. Using rapid, reversible optogenetic inhibition during a head-fixed task in which mice reach, grasp, and eat a food pellet, sudden cortical inhibition blocked initiation or froze execution of the skilled prehension behavior while leaving untrained forelimb movements intact. Unexpectedly, kinematically normal prehension occurred immediately after inhibition ended, even during rest periods without cue or pellet. This rebound prehension appeared only in trained, food-deprived animals, suggesting that a motivation-gated motor engram sufficient to evoke prehension is activated at the end of inhibition. These results demonstrate that cortical activity is both necessary and sufficient to produce a learned skilled movement.
“Cortex commands the performance of skilled movement” by Jian‑Zhong Guo et al., eLife. Published online December 2, 2015. doi:10.7554/eLife.10774