Fiberless optogenetics

Optogenetics, which relies on the use of photons to manipulate cellular and subcellular processes, has emerged as an important tool that has transformed several fields including neuroscience. Improvement of optogenetic topographies, together with integration with complementary tools such as electrophysiology, imaging, anatomical and behavioral analysis, facilitated this transformation. However, an inherent challenge associated with optogenetic manipulation of neurons in living organisms, such as rodents, is the requirement for implanting light-delivering optical fibers. This is partly because the current repertoires of light-sensitive opsins are activated only by visible light, which cannot effectively penetrate biological tissues. Insertion of optical fibers and subsequent photo-stimulation inherently damages brain tissue, and fiber tethering can constrain animal behavior. To overcome these technical limitations, we and other research groups recently developed minimally invasive “fiberless optogenetics,” which uses particles that can emit visible light through up-conversion luminescence in response to irradiation with tissue-penetrating near-infrared light. Fiberless optogenetics also offers the opportunity to control neural function over longer time frames in freely behaving animals. In this chapter, we discuss the development of fiberless optogenetics and its application in neuroscience and beyond.