Optogenetics

Optogenetics: Using light to control cells

Optogenetics is a technique that involves the use of light to control cell function. Cells are first genetically modified to express light-sensitive ion channels, called opsins. Then, light can be used to activate the opsin. The most well-known opsins are light-gated ion channels that can control the excitability of the cell membrane. When activated by the opsin-specific wavelength of light, the channels open allowing ions to flow across the cell membrane to either excite or inhibit the cell. Optogenetics enables precise control over a targeted cell population.

Many opsins, many options

Since the first microbial opsin was introduced into mammalian neurons in 2005, many different opsins have been used to control the excitability of electroactive cells such as neurons and cardiomyocytes. Each opsin is sensitive to a specific wavelength range, or color of light and induces a precise biological event.

Channelrhodopsin (ChR2), for example, is activated by blue light. When ChR2 opens, positive cations (like sodium and calcium), flow into the cell, depolarizing or exciting the cell. In contrast, halorhodopsin and archaerhodopsin both inhibit cell excitability by hyperpolarizing the cell in response to yellow or green light, respectively. With optogenetics, you can turn on and off cells like a light switch.

The timing of these light-activated events is fast, facilitating highly precise control. First generation opsins, such as channelrhodopsin, open and close in milliseconds, ideal for kicking off an action potential. Second generation opsins have fined tuned kinetics for even faster, more precise control or slower, longer-lasting inhibition. For example, step-function opsins stay open until another pulse of light switches them off.

Optogenetics can precisely control which cells are turned on or off by employing different gene promoters for opsin expression. Opsins can be expressed in all neurons or used to control specific subpopulations. Unlike electrical stimulation, which excites all nearby cells, optical stimulation can be finely targeted to the cells expressing the opsins responsive to a narrow band of light wavelengths.

In summary, optogenetics is a powerful toolbox for precise control over targeted cell populations at fast time scales. Superior spatial and temporal control, reversibility, and easy stimulus delivery make exploring complex biology simpler than ever before.

More than just ion channels

As the field has advanced, opsins have been used to control more than just ion flow. Light-activated gene expression with light-inducible transcription factors can control the proteins made by cells. The combination of optogenetics with CRISPR provides even greater control over CRISPR/Cas9 gene editing.

Opsins have also been incorporated into many biochemical and intracellular signaling pathways to control key protein functions. MAPK and PI3K pathways, Rho family GTPase activation, apoptosis, and protein trafficking can now all be precisely controlled by light.

Shining light in vitro

Sophisticated biology like optogenetics demands sophisticated technology to explore it. In vitro technology relied on single wavelength lasers and custom lab-specific tools while many in vivo technologies were quickly developed for optical stimulation. The Lumos Optical Stimulation system is the first-of-its-kind multiwell optical stimulator with the ability to deliver up to four wavelengths of light per well with microsecond precision. From controlling the excitability of your neurons to pacing the beating of your cardiomyocytes, discover how the Lumos and optogenetics can revolutionize your assay.