Mesoscale Ca²⁺ Imaging During Locomotion

Locomotion is one of the most basic of animal behaviors, providing animals with the ability to actively explore and interact with the external world. While the basic cyclic pattern of locomotion is created in the spinal cord by central pattern generators, virtually all regions of the nervous system are not only engaged but play important roles in locomotion. During locomotion, there is widespread modulation of neurons in the cerebral cortex, including premotor, primary motor, primary sensory, parietal, and retrosplenial cortices. Cerebral cortical activity during locomotion serves to adjust the parameters of locomotion and to process somatosensory, visual, and auditory stimuli more effectively. Therefore, full comprehension of locomotion requires monitoring the widespread modulation of neuronal activity throughout the cerebral cortex to understand the neural dynamics and changing interactions between regions. A similar approach is needed for other brain regions involved in controlling locomotion such as the cerebellar cortex. With the development of new generations of genetically encoded Ca²⁺ indicators and improved tools for optical imaging, mesoscale Ca²⁺ imaging provides a powerful approach for monitoring neuronal activity over large regions at relatively high spatial and temporal resolution. Our recent mesoscale Ca²⁺ imaging in the cerebral cortex demonstrates the dynamic interactions between cortical regions and changing states from rest to walk. This chapter describes our methods for mesoscopic Ca²⁺ imaging in the cerebral cortex during locomotion and the extension of the technique to the cerebellar cortex.