Optogenetics is a technique for controlling neuronal activity and signalling with light. It works by genetically targeting neurons to express light-sensitive ion channels and pumps. When these opsins are stimulated with particular wavelengths of light, they control the flow of ions across neuronal membranes, depolarizing or hyperpolarizing the cells. This allows researchers to stimulate or inhibit targeted neurons with exquisite spatial and temporal precision using fiber-optic technologies and lasers or LEDs. Optogenetics has revolutionized our ability to probe neuronal circuit function and investigate the roles of specific neuronal populations in vivo.

The Basic Components of Optogenetics

Optogenetics employs microbial opsins, which are light-sensitive membrane proteins found in algae and bacteria. The two main opsins utilized are channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR). ChR2 is a cation channel that opens upon blue light stimulation, causing neuronal depolarization. NpHR is a chloride pump activated by yellow light, generating neuronal hyperpolarization. Genes encoding these opsins are delivered to neurons using viral vectors. Viruses like AAV infect neurons and integrate the opsin gene into the genome, forcing long-term opsin expression selectively in targeted neuronal populations. Engineers have also developed genetically-encoded indicators that change fluorescent properties upon neuronal firing, allowing visualization of neuronal activity with high spatial and temporal resolution.

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