Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.McGovern Institute for Brain Research at MIT (Razin Fellowship)United States. Defense Advanced Research Projects Agency. Living Foundries Program (HR0011-12-C-0068)Harvard-MIT Joint Research Grants Program in Basic NeuroscienceHuman Frontier Science Program (Strasbourg, France)Institution of Engineering and Technology (A. F. Harvey Prize)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD002002)National Institute of General Medical Sciences (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (Career Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS0848804)Society for Neuroscience (Research Award for Innovation in Neuroscience)Wallace H. Coulter FoundationNational Institutes of Health (U.S.) (RO1 MH091220-01)Whitehall FoundationEsther A. & Joseph Klingenstein Fund, Inc.JPB FoundationPIIF FundingNational Institute of Mental Health (U.S.) (R01-MH102441-01)National Institutes of Health (U.S.) (DP2-OD-017366-01)Massachusetts Institute of Technology. Simons Center for the Social Brai

Dynamic illumination of spatially restricted or large brain volumes via a single tapered optical fiber

Optogenetics promises spatiotemporal precise control of neural processes using light. However, the spatial extent of illumination within the brain is difficult to control and cannot be adjusted using standard fiber optics. We demonstrate that optical fibers with tapered tips can be used to illuminate either spatially restricted or large brain volumes. Remotely adjusting the light input angle to the fiber varies the light-emitting portion of the taper over several millimeters without movement of the implant. We use this mode to activate dorsal versus ventral striatum of individual mice and reveal different effects of each manipulation on motor behavior. Conversely, injecting light over the full numerical aperture of the fiber results in light emission from the entire taper surface, achieving broader and more efficient optogenetic activation of neurons when compared to the standard flat-faced fiber stimulation. Thus, tapered fibers permit focal or broad illumination that can be precisely and dynamically matched to experimental needs

Laser/Light Applications in Neurology and Neurosurgery

Applications of light in neurology and neurosurgery can be diagnostic or therapeutic. Neurophotonics is the science of photon interaction with neural tissue. Photodynamic therapy (PDT) has been attempted to destroy infiltrative tumor cells in tissue. Spatially modulated imaging (MI) is a newly described non-contact optical technique in the spatial domain. With this technique, both quantitative mapping of tissue optical properties within a single measurement and cross sectional optical tomography can be achieved rapidly. The ability to control the activity of a defined class of neurons has the potential to advance clinical neuromodulation

A guide to in vivo optogenetic applications for cerebellar studies

The mammalian cerebellum consists of a superficial cortex and centrally located output nuclei, which together with brainstem nuclei are organized in a modular fashion. Regardless of the function, these cerebellar modules consist of the same cell types, and their connectivity has been unraveled to some detail using electrical stimulation experiments. To unravel the highest level of detail, cell-specific stimulation experiments are warranted, which cannot be accomplished using electrical stimulation. To reach this unprecedented level of specificity, optogenetic applications are now being implemented in cerebellar studies. Due to the extensive knowledge about cell-specific markers in both the cerebellar cortex and the cerebellar nuclei, optogenetics can be applied cell specifically. Ideally the anatomical and electrophysiological characteristics of the cerebellum can be utilized for designing future optogenetic studies. In this chapter we review the opportunities and pitfalls for optogenetic studies in the cerebellum. We provide insights into the technical issues at hand and which solutions are currently available