Optogenetics has been widely used to study the physiology of the brain and nervous system in order to better map and understand neuronal circuits. Photogenetic tools are also used to trigger and study some behavioral responses of model organisms, such as mice, zebrafish and fruit flies. These tools have played an important role in the research of nervous system diseases and helped scientists better understand Parkinson's disease, depression, drug addiction and so on.
Opsin is an optically gated ion channel or pump that can absorb light at a specific wavelength. After being activated by light, these channels and pumps respond by opening or closing, guiding ion flow in and out of the cell. Scientists have identified a variety of naturally occurring microbial opsins that respond to different wavelengths of light, such as blue or yellow light. Researchers have used genetic engineering to improve these natural opsins by inducing point mutations to change the absorption spectrum or adding transport signals to locate opsins on the cell membrane.
Microbial opsins, such as Channelrhodopsins, Halorhodopsins and Archaerhodopsins, can be expressed in specific cells, allowing precise temporal and spatial control of these cells by turning on and off the light source.
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One of the earliest microbial opsins used as optogenetic tools is the widely used channelrhodopsin-2 (ChR2) from Chlamydomonas reinhardtii. ChR2 is a membrane channel that opens in response to blue light and allows cations to flow into cells. Variants of rhodopsin have been designed or identified to increase spectral and kinetic properties and improve expression and membrane targeting in host cells.
ChR variants have been engineered with enhancements such as:
Increased photocurrent amplitude-ChR2(H134R), C1V1(t/t), ChIEF
Increased channel (on/off) kinetics-ChETA, C1V1(t/t), ChrimsonR
Red-shifted peak action spectra-VChR1, C1V1(t/t), Chrimson, ChrimsonR, Chronos
Halorhodopsins is an optically gated inward chloride pump isolated from salt bacteria. The wild-type salt rhodopsin called NpHR (from Natronomonas pharaoni) can cause cell hyperpolarization (inhibition) when triggered by yellow light, thereby inhibiting the function of neurons.
Halorhodopsins variants have been engineered with enhancements such as:
Increased photocurrent amplitude-eNpHR, eNpHR2.0, eNpHR3.0
Red-shifted peak action spectra-Jaws
Archaerhdopsin-3 (arch) from halorubrum sodomense is also commonly used to inhibit neurons in optogenetic experiments. Arch is a light activated outward proton pump that hyperpolarizes (inhibits) cells when triggered by green and yellow light.
Archvariants have been engineered with enhancements such as:
Increased light sensitivity-ArchT
Increased photocurrent amplitude-eArch3.0, eArchT3.0
Optogenetics Applied in System Neuroscience
Optogenetics Applied in Epilepsy
Optogenetics Applied in Retinal Dystrophies
Optogenetic Applied in Auditory
Optogenetics Applied in Cardiac
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