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Monthly Archives: November 2012
The ability to deliver light into the brain for the purpose of controlling neural activity or other biological processes, optogenetics, has opened up new frontiers in both basic neuroscience and neuroengineering. One arena of great activity is in the use of microbial opsins such as channelrhodopsins, halorhodopsins, and archaerhodopsins to make neurons activatable or silenceable by light, thus enabling assessment of the causal contribution of specific neurons, brain regions, and neural pathways to normal and abnormal behaviors and neural computations. To date, numerous in vivo studies have used optical fibers, and fiber-electrode hybrids, to deliver visible light into brain targets in which neurons express opsins, but an optical fiber can target just a single region. An implantable probe capable of delivering light to arbitrary points in a 3-dimensional volume would enable more versatile optical control, opening up the ability to deliver patterned light to manipulate neural activity in distributed brain circuits.
The Boyden lab recently developed a linear probe comprising a set of integrated microwaveguides running in parallel to each other, microfabricated on a single substrate and capable of delivering light independently to multiple brain targets along the probe axis. In a paper published in Optics Letters, they now extend … Continue reading
If we could control the activity of any intracellular protein of interest with light, it would revolutionize how we study biology and engineer gene- or cell-based therapies. For instance, optical protein control would allow testing of protein functions in cells with high spatiotemporal precision, so we can observe how protein activation at specific times and places affects downstream biochemical reactions and cellular behavior, without secondary effects from chronic or ubiquitous activation. Optical protein control would also allow four-dimensional regulation of cellular proliferation, survival, or differentiation in tissues or animals for basic research or therapy. Thus controlling a wide variety of proteins with light is one of the major long-term goals of optogenetics.
Meeting this challenge will require the development of easily generalizable methods for optical control of protein activity. Considerable efforts have been made to adapt natural light-responsive signaling proteins to regulate specific proteins of interest. In recent years, phytochrome-PIF, cryptochrome-CIB, and FKF-gigantea light-dependent interactions from plants have been adapted to control heterodimerization of proteins in mammalian cells. The LOV domain from phototropin has also been used to create single-chain photoactivatable proteins via light-modulated allosteric mechanisms. However, these methods have certain disadvantages. Light-controlled heterodimerization can not effectively control activities of … Continue reading
Numerous applications enabled by optogenetic tools require the delivery of different light profiles within tissue. In some instances, wide-field illumination is needed to blanket a region of a specific brain layer, while cell body-size beams are necessary in other cases to achieve highly-selective localized stimulation; in addition, spatiotemporal patterning or multi-level access of light may be incorporated. In a recent paper published in Biomedical Optics Express, Abaya, et al. presented a novel device structure that facilitates three-dimensional deep-tissue light penetration with capabilities for simultaneous spatiotemporal modulation with different wavelengths. This device consists of > 1 mm length needle-shaped waveguides that circumvent intrinsic tissue absorption and scattering. This array can be adapted to a wide variety of illumination systems (e.g., microscope, μLED arrays, optical fibers, collimated beams, spatial light modulators) and can potentially facilitate the advancement of a broad range of applications utilizing optical neural stimulation.
The waveguide array is micromachined from fused silica/quartz wafers, which are transparent to visible and near-infrared wavelengths. First, bevel blades are used with a dicing saw to create arrays of pyramids as tips for the array. Next, the shanks are formed by dicing down material in between the pyramids to produce waveguides having a pyramidal … Continue reading