ABSTRACT

Brain imaging techniques are essential for advancing our understanding of the basic principles underlying neural circuit function, connectivity across neuronal populations and entire brain regions, the functional development of the early nervous system, and the mechanisms of neural circuits underlying behavior. The central tenet of imaging a nervous system in action is the spatiotemporal scale at which neuronal activity occurs, thereby setting it apart as a unique challenge rarely encountered in other bio-imaging scenarios. Additionally, imaging the activity from a population of neurons in the intact brain of a behaving animal makes this task even more challenging, which has motivated researchers to engage a variety of advanced techniques to push through this boundary. Among optical methods, light-sheet microscopy is well-positioned to tackle the numerous challenges encountered in functional imaging of the nervous system, as it provides a unique combination of strengths: light-sheet microscopy offers high spatial resolution, high imaging speed, good physical coverage of partially opaque specimens, and low energy load on the specimen for long-term imaging under physiological conditions. In this chapter, we discuss recent efforts in recording neuronal activity using light-sheet microscopy and the opportunities it has carved in deepening our understanding of the inner workings of the brain.