Abstract
Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used in studying brain function. A multitude of optogenetic tools for neuroscience have been created that, for example, enable the control of action potential generation via light-activated ion channels. Other optogenetic proteins have been used in the brain, for example, to control long-term potentiation or to ablate specific subtypes of neurons. In in vivo applications, however, the majority of optogenetic tools are operated with blue, green, or yellow light, which all have limited penetration in biological tissues compared to red light and especially infrared light. This difference is significant, especially considering the size of the rodent brain, a major research model in neuroscience. Our review will focus on the utilization of red light-operated optogenetic tools in neuroscience. We first outline the advantages of red light for in vivo studies. Then we provide a brief overview of the red light-activated optogenetic proteins and systems with a focus on new developments in the field. Finally, we will highlight different tools and applications, which further facilitate the use of red light optogenetics in neuroscience.
Highlights
Optogenetics is a field of science focusing on controlling cellular functions with light-sensing proteins (Deisseroth et al, 2006)
Neuroscience has always been the major target for optogenetic systems, and they are well established as neuroscientific research methods (Mahmoudi et al, 2017)
The spatial resolution is a combination of gene technology and the accurate focusing of the Abbreviations: AAV, adeno-associated virus; CBCRs, cyanobacteriochromes; Gradient index (GRIN), gradient index; EEG, electroencephalography; PBM, photobiomodulation; PDB, Protein Data Bank; Phytochrome-Interacting Factor (PIF), phytochrome-interacting factor; NIR, near-infrared; MIR, magnetic resonance imaging; Upconversion nanoparticles (UPNC), upconversion nanoparticles
Summary
Optogenetics is a field of science focusing on controlling cellular functions with light-sensing proteins (Deisseroth et al, 2006). Blue light can activate several natural pathways in neural cells even without applied optogenetic actuators (Tyssowski and Gray, 2019) When it comes to red light, the mechanisms behind photobiomodulation (PBM) can cause similar problems. Different widely used opsin proteins are activated by either blue or red light (Nagel et al, 2003; Chuong et al, 2014) Their chromophore, a derivate of vitamin A called retinal, seems to be available in most in vivo models in broad utilization in neuroscience (Deisseroth, 2015). Most red light-driven optogenetic actuators utilize different bilin molecules as their chromophores, the availability of which varies between the target cells (Chernov et al, 2017). The majority of the new red light-sensing actuator systems outside of opsins are based on the plant phytochrome B and its binding partner PIF.
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