Abstract
Advances in imaging tools have always been a pivotal driver for new discoveries in neuroscience. An ability to visualize neurons and subcellular structures deep within the brain of a freely behaving animal is integral to our understanding of the relationship between neural activity and higher cognitive functions. However, fast high-resolution imaging is limited to sub-surface brain regions and generally requires head fixation of the animal under the microscope. Developing new approaches to address these challenges is critical. The last decades have seen rapid progress in minimally invasive endo-microscopy techniques based on bare optical fibers. A single multimode fiber can be used to penetrate deep into the brain without causing significant damage to the overlying structures and provide high-resolution imaging. Here, we discuss how the full potential of high-speed super-resolution fiber endoscopy can be realized by a holistic approach that combines fiber optics, light shaping, and advanced computational algorithms. The recent progress opens up new avenues for minimally invasive deep brain studies in freely behaving mice.