— Last updated on February 27, 2025 —
Optogenetics is a technique that expresses light-sensitive microbial proteins in eukaryotic cells to control their activity. In 2005, Deisseroth’s lab reported for the first time the use of the microbial protein Channelrhodopsin-2 (ChR2) in neurons. Since then, optogenetics has become an essential technique in neuroscience.
These light-sensitive proteins are ion channels called opsins, which encoding genes are commonly delivered into neurons through viruses that contain cell-specific promoters or by using Cre-dependent viruses (post) with Cre animals (post). Next, researchers can use light (via a microscope or an optical fiber) to activate the opsins expressed only in the neurons of interest (video 1).
There is a wide range of kinetic opsin variants, but we can differentiate three main classes: channelrhodopsins, halorhodopsins, and bacteriorhodopsins (see cover image). Generally, channelrhodopsins are cation channels and induce neuronal excitation (video 1), halorhodopsins are anion channels and inhibit neuronal activity, whereas bacteriorhodopsins are a family of proton pumps.
Most opsins are usually activated by either blue or green light. However, protein engineering has achieved opsins such as ChRMine or Chrimson activated by red lights, and even bidirectional (inhibition and excitation) dual-color opsins like BiPOLES.
Optogenetics has been proven to precisely modulate neural circuits and behavior in many animal models, including non-human primates. These experiments have demonstrated the causal role of neurons and brain areas during behaviors. For instance, Deisseroth’s and Yuste’s groups were able to activate a small group of visual neurons and created “hallucinations” in mice using optogenetics. Meanwhile, Tonewaga’s lab manipulated hippocampal neurons to either activate or incept false memories in mice. Optogenetics might also have the potential to partially restore vision in humans, as suggested by a pilot study in 2021 (video below from Sahel et al., 2021).
In the next few years, new developments such as non-invasive gene delivery, reduced photodamage, and more sensitive opsins (that can be activated from outside the skull) will bring new discoveries and, maybe, the use of optogenetics for routine clinical applications.
Resources to learn more
▪ FPbase. Database for fluorescent proteins (FPs), including some opsins.
▪ Optogenetics guide and Plasmids for Optogenetics Research from Addgene.
▪ Optogenetics training series from the Society for Neuroscience.
▪ Optogenetics Resource Center from The Deisseroth Lab.
▪ Equipment for optogenetics
▪ Doric lenses
▪ Prizmatix
▪ Thorlabs
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