Role of mouse motor cortex in the behavioral response to unpredictable visual feedback

Movement is the way by which we interact with the world. This often only becomes apparent in case of motor apparatus dysfunction such as in neurological conditions of movement disorders highlighting how seemingly effortless the nervous system performs movement generation. Moreover, many animal species are capable of moving in a stunningly vast array of ways which underscores the requirement for sophisticated degrees of control. Furthering insight into motor control therefore underlies a fascination for the complexity of the nervous system as well as a substantial medical interest. To understand the role of motor cortex, a high-level brain area, in the control of sensory guided movements, I first trained head-fixed mice to navigate a two-dimensional virtual reality environment with occasional perturbations of the expected visual feedback. During learning, I used activity manipulation by optogenetics to understand the involvement of motor cortex in active behavior. Additionally, using activity recording by two-photon calcium imaging in genetically defined projection cell types, I probed for neuronal activity patterns potentially mediating this behavior. I found that motor cortex is a critical brain area for execution of visually guided behavior which mediates the learning of the navigation task. Activity recordings yielded a myriad of neuronal responses correlating with the mouse behavior, often multiplexed within the same cell. Critically, activity patterns during spontaneously executed, expected behavior differed from those during reactive behavior induced by unexpected perturbations of the virtual environment. These differences in neuronal activation could underlie the behavioral effects observed during optogenetic activity manipulations. Finally, I observed cell type-specific, learning-related changes. Notably, presumed motor output mediating cells increased in activation as mice became more efficient at executing the task. I discuss these findings in the context of recent theories of brain function suggesting that the nervous system not only predicts the dynamics of the subject’s environment but also generates movement in reaction to future predicted body states