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Optogenetic Modulation of Neural Circuits
Published in Francesco S. Pavone, Shy Shoham, Handbook of Neurophotonics, 2020
Mathias Mahn, Oded Klavir, Ofer Yizhar
Optogenetic inhibition was first accomplished using the light-driven chloride pump halorhodopsin (HR) from Natronomonas pharaonis (Scharf and Engelhard, 1994; Zhang et al., 2007). The red-shifted action spectrum of this microbial rhodopsin allows multiplexed excitation and inhibition when combined with the blue light-sensitive ChRs. Activation of the proton-pumping bacteriorhodopsin (Gradinaru et al., 2010) and archaerhodopsin (Chow et al., 2010) can also hyperpolarize neurons, effectively inhibiting them due to the outward-directed movement of protons during illumination of these tools. Additional engineering contributed to improved photocurrent amplitudes (and thereby more efficient inhibition) mediated by improved membrane targeting of these proteins, which originate in prokaryotes and therefore initially failed to express robustly in mammalian neurons (Gradinaru et al., 2010; Mattis et al., 2011). The membrane targeting-enhanced versions of halorhodopsin (eNpHR3.0) and archaerhodopsin (eArch3.0) have therefore become the most widely used tools for optogenetic silencing of neurons, and numerous studies have utilized these tools for temporally precise and reversible optogenetic inhibition (Fenno et al., 2011). As with the excitatory ChRs, the anion-pumping HR displays a pronounced peak upon initial illumination, which then decays to a steady-state photocurrent, a behavior that should be taken into account when designing long-term inhibition experiments (Mattis et al., 2011; Goshen et al., 2011). Importantly, it has been shown that ion-pumping microbial rhodopsins can shift the concentrations of intracellular ions to non-physiological levels. In the case of halorhodopsin, this can lead to accumulation of chloride in the neuron, inducing changes in the reversal potential of GABAergic synapses (Raimondo et al., 2012) while archaerhodopsin was shown to increase the intracellular pH, inducing action potential independent Ca2+ influx and elevating spontaneous vesicle release in presynaptic terminals (Mahn et al., 2016).
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]