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Genetically Encoded Activity Indicators
Published in Francesco S. Pavone, Shy Shoham, Handbook of Neurophotonics, 2020
Channelrhodopsins are widely used as optogenetic actuators. The photocurrent of these light-activated ion channels and their engineered derivatives is used in optogenetics to actuate membrane potential (Deisseroth and Schnitzer, 2013). The reversal, namely modulation of light output by membrane potential, would not be expected from the principal function of rhodopsins. The finding that Archaerhodopsin 3 (Arch) exhibits a voltage-dependent near-infrared fluorescence therefore came with much surprise to the field (Kralj et al., 2011). The excitement about the fast kinetics of the optical response to membrane voltage changes of Arch was dampened by its low quantum yield (QY 10−3) and the resulting need to use very high illumination densities. This issue has subsequently been addressed by the combination of FPs and opsins with the latter acting as voltage-dependent quenchers (Gong et al., 2014; Zou et al., 2014), and these FRET-opsin GEVIs have been generated with several FP color variants. Moreover, site-directed mutagenesis optimized the voltage dependent steps in the Arch photocycle, yielding better GEVIs that along with specialized microscopes yielded high SNR voltage recordings from single neurons in a brain slice and in vivo (Gong et al., 2015; Werley et al., 2017).
Flexible and Stretchable Devices for Human-Machine Interfaces
Published in Muhammad Mustafa Hussain, Nazek El-Atab, Handbook of Flexible and Stretchable Electronics, 2019
Irmandy Wicaksono, Canan Dagdeviren
The previous examples of flexible 2D devices provide non- to minimally invasive approaches to neural reading. Yet, there are some cases when it is necessary to penetrate further to target specific regions for simultaneous neural reading and modulation. New materials and fabrication strategies have motivated researchers to develop a 3D out-of-plane structure of probes or injectrodes that are bio-compatible and compliant with the mechanical properties of the nerves. Figure 18.22 shows many existing platforms and techniques of multi-modal neural interfacing that can penetrate to delicate regions or conform to the curvilinear surface of the brain, spinal cord, and peripheral nerves while alleviating tissue damage and foreign-body reaction (Lacour et al. 2016). Besides conventional electrical stimulation that uses an electric current to excite surrounding neurons, and delivery of biochemical agents to affect neurotransmission, a new modality for neuronal activations through the flow of photons has emerged. Optical stimulation through optogenetics provides a means to activate specific neurons that exhibit light-responsive ion channels by genetically modifying them with reagents such as channelrhodopsin (Grill et al. 2009; Fenno et al. 2011).
Bioelectrical coordination of cell activity toward anatomical target states
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Celia Herrera-Rincon, Justin Guay, Michael Levin
One of the more intriguing developments in the last decade for direct control of membrane voltage is the development of optogenetics (Boyden et al. 2005, Wyart et al. 2009, Arrenberg et al. 2010, Boyden 2011, Bernstein et al. 2012). The first applications made use of endogenous proteins derived from a variety of plants and lower organisms, which enabled light-triggered ion flow. The first application of this kind was channelrhodopsin-2, derived from algae, which when ectopically expressed can activate neurons by permitting cation flux in response to blue light (Boyden et al. 2005). Halorhodopsin from the archaebacterium Natronomonas pharaonis hyperpolarizes cells and has been used in neural suppression studies (Han and Boyden 2007). The light-sensitive H+ pump archaerhodopsin has been exploited in amputated tails of tadpole to restore regeneration in non-regenerative developmental stages (Adams et al. 2007). Ongoing work is resulting in the development of magnetically (Long et al. 2015) and acoustically (Ibsen et al. 2015) triggered ion channels, which will help transition this technology to practical use in thick, optically opaque regenerating structures.
Mechanism of peripheral nerve modulation and recent applications
Published in International Journal of Optomechatronics, 2021
Heejae Shin, Minseok Kang, Sanghoon Lee
Optogenetic neuromodulation is a technology that has a higher selectiveness than electrical neuromodulation.[62] This technology modulates nerves using a photoreceptor protein called opsin, which can open and close ion channels in cells according to specific wavelengths of light. There are different types of opsin that respond to specific wavelengths of light.[63–65] One of these opsins, channelrhodopsin is expressed in the sodium ion channel. When the blue light is irradiated, sodium ion channels are opened, allowing Na+ ions to enter the cell and induce depolarization to cause excitation (Figure 3(a)). One of the types of Channelrhodopsin, channelrhodopsin-2 (ChR2) has the maximum relative activity at a wavelength of 470 nm.[66] Conversely, as opsins that cause inhibition rather than excitation, archaerhodopsin and halorhodopsin exist. ArchT1.0 and eArch3.0 of archaerhodopsin are expressed in the proton pump and when the green light is irradiated, the pump is activated to move the H+ ions from inside to the outside of the cell, inducing hyperpolarization, which in turn causes inhibition. For ArchT1.0 and eArch3.0, the relative activity is maximized at 566 nm wavelengths, respectively. NpHR, a type of halorhodopsin, is expressed in the chloride ion channel and when the yellow light is irradiated, the chloride ion channel opens, and Cl- ions enter the inside of the cell and cause hyperpolarization. For NpHR, the relative activity is maximum at 589 nm. However, in the case of these opsins, since the wavelength range of the activated light overlaps (Figure 3(b)), there is a limitation that several types of opsins cannot be used in target neurons. To compensate for this limitation, research is underway on opsins whose wavelength ranges do not overlap, such as C1V1 and red-active ChR.[67]