Austin R. Graves, Nuo Li, Jian-Zhong Guo, Allen T. Lee, Kristin Branson, Brett D. Mensh, Jihong Zheng, Wendy W Guo, James W Phillips, Juan Rodríguez-González, Adam W. Hantman, and John J. Macklin
Mammalian cerebral cortex is accepted as being critical for voluntary motor control, but what functions depend on cortex is still unclear. Here we used rapid, reversible optogenetic inhibition to test the role of cortex during a head-fixed task in which mice reach, grab, and eat a food pellet. Sudden cortical inhibition blocked initiation or froze execution of this skilled prehension behavior, but left untrained forelimb movements unaffected. Unexpectedly, kinematically normal prehension occurred immediately after cortical inhibition, even during rest periods lacking cue and pellet. This ‘rebound’ prehension was only evoked in trained and food-deprived animals, suggesting that a motivation-gated motor engram sufficient to evoke prehension is activated at inhibition’s end. These results demonstrate the necessity and sufficiency of cortical activity for enacting a learned skill. DOI: http://dx.doi.org/10.7554/eLife.10774.001, eLife digest Many of the movements that humans and other animals make every day are deceptively complex and only appear easy because of extensive practice. For example, picking up an object involves several steps that must be precisely controlled, including reaching towards the item and holding it using the right amount of pressure to not crush it or drop it. Part of the brain called the motor cortex is thought to be important for learning and controlling these skilled movements, but its exact role in these processes is not clear. A technique called optogenetics allows the roles of individual parts of the brain to be studied by rapidly altering their activity, whilst minimizing the likelihood that the brain will compensate for these changes. By genetically modifying animals to produce light-sensitive channel proteins in certain brain cells, the activity of particular regions of the brain can be controlled by shining light onto them. Guo et al. have now used optogenetics to control the motor cortex as the mice performed a task they had been trained to do – reaching for and picking up a food pellet. Suddenly shutting down the motor cortex at the start of a trial prevented the mice from starting the task, and shut down part way through the task caused the front limbs of the mice to freeze in midair. However, only the learned, skilled task was frozen by motor cortex shutdown; mice could still move their limbs normally if the motor cortex was instead shut down during routine movements. When the cortex was reactivated, the mice instantly resumed trying to pick up the food pellet. Unexpectedly, even during rest periods when there was no food pellet and the mice were just waiting for the experiment to begin, turning the motor cortex off and then back on again suddenly caused the mice to perform the complete grabbing motion. This implies that the cortical activity evoked at the end of inactivation acts to trigger the full movement sequence. This was particularly likely to occur if the animal had been deprived of food before the test or was particularly well trained, but did not depend on the position of the limb. Overall, Guo et al.’s work opens the question of how the instructions that describe the learned movement are encoded within the motor cortex and its downstream networks. Future studies could also investigate how learning a set of movements affects the structure of cortical neurons and their connections, thus suggesting how these memories are stored. DOI: http://dx.doi.org/10.7554/eLife.10774.002