Making Sense of Optogenetics

Abstract

This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically-defined neurons with light. Cells are first genetically engineered to express a light-sensitive opsin, which is typically an ion channel, pump, or G protein–coupled receptor. When engineered cells are then illuminated with light of the correct frequency, opsin-bound retinal undergoes a conformational change that leads to channel opening or pump activation, cell depolarization or hyperpolarization, and neural activation or silencing. Since the advent of optogenetics, many different opsin variants have been discovered or engineered, and it is now possible to stimulate or inhibit neuronal activity or intracellular signaling pathways on fast or slow timescales with a variety of different wavelengths of light. Optogenetics has been successfully employed to enhance our understanding of the neural circuit dysfunction underlying mood disorders, addiction, and Parkinson’s disease, and has enabled us to achieve a better understanding of the neural circuits mediating normal behavior. It has revolutionized the field of neuroscience, and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components.

Light‐Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology

“…[37] The most powerful and widely used photoreceptor systems in neural optogenetics (ion flux-based optogenetics) come from the opsin photoreceptor family. [38] Type I opsins are of great interest in the field of neural optogenetics, where they are used to control the function of neurons, because they are easier to engineer and express in mammalian cells (as a single-component protein), and have faster kinetics than type II opsins. They can be categorized into two major classes: microbial opsins (type I) and invertebrate/vertebrate opsins (type II).…”

“…[43] Opsins are G-protein-coupled Opsin-based photoreceptors: a) natural G-protein-coupled (GPC) photoreceptors such as melanopsin or animal rhodopsin signal through endogenous pathways. [38] So far, more than a thousand animal opsins have been identified, and they can be divided into seven subfamilies. Gαq subunit-dependent signaling is linked to increased levels of inositol-3-phosphate (IP3) and diacylglycerol (DAG), whereas Gαt signaling mainly results in lowered cGMP levels that trigger subsequent signal amplification steps in photoreceptor cells of the mammalian retina.…”

“…These membrane-bound GPC photoreceptors are retinal-dependent. [45] During signal transduction, exposure to light induces isomerization of the retinal chromophore from 11-cis-retinal to all-trans-retinal, which subsequently changes the conformation of the melanopsin receptor [38] (Figure 1b). While microbes incorporate mainly all-transretinal that is activated to 13-cis-retinal in melanopsin, mammals use 11-cis-retinal that is transformed into its all-trans-conformer upon illumination.…”

Microfabricated Probes for Studying Brain Chemistry: A Review

“…Microfabrication already offerss ignificant boons to neural probe research that have been discussed in previouss ections of this review.N onetheless,w ef eel significant room remains to extend the conversation to the topic of optogenetics. [181][182][183][184][185] The capacity to genetically prime and then optically stimulate isolated neuron clusters is particularly attractive for micronscale probesd esigned to access small brain structures. Optogenetic experiments often employed optical fibers connected to al ight source, such as al aser or LED, to supply the light sufficientf or stimulation.…”

Exploiting modal demultiplexing properties of tapered optical fibers for tailored optogenetic stimulation

“…TFs also allowed for site selective light delivery in the striatum to control specific locomotion behavior, on the base of different modal subsets injected into the fiber to illuminate ventral or dorsal striatum using only one and minimally invasive implant 21 . However, to the best of our knowledge, no studies directly link the modal subsets guided into the fiber with the light delivery geometry from a tapered optical fiber for optogenetics applications, and no direct assessment of TFs site-selective light-delivery performances at longer wavelengths has been reported, a crucial aspect for using this technology with a broad set of opsins [24][25][26] .…”