Shining Light on the Evolution of Optogenetics

Since its emergence in the early 2000s, optogenetics has revolutionized the study of the brain by enabling researchers to control the activity of specific neurons using light-sensitive proteins and precisely timed flashes of light. What began as a powerful experimental approach in model organisms such as fruit flies and mice has steadily advanced toward clinical applications in humans, opening new possibilities for treating neurological and sensory disorders. In celebration of The Scientist’s 40^th anniversary, we searched through our archives to highlight our coverage of the evolution of optogenetics over the years.

2005: From Visualizing to Stimulating the Brain

Before optogenetics emerged, researchers studying neural signaling relied largely on voltage- and calcium-sensitive dyes, as well as probes designed to detect changes in pH. Combined with the use of green fluorescent protein (GFP), these methods were used to visualize cells and monitor neural activity. However, they largely allowed researchers only to “read” neural systems.

The next challenge was learning how to directly interact with and manipulate those systems. In 2005, Karl Deisseroth, a neuroscientist and physician, and colleagues at Stanford University developed a new optical method: They paired channelrhodopsin, a light-sensitive cation channel isolated from green algae, with a GFP variant, and expressed the construct in cultured rat neurons that could be stimulated by light. This laid the foundation for optogenetics, giving researchers the ability not only to observe neural activity, but also to precisely control—or “write”—the neural circuits.

2011: The Foundations of Optogenetics

In this first-person account, neuroscientist Ed Boyden reflected on the origins of optogenetics and the early efforts to develop tools capable of controlling the electrical activity of specific neuron types within intact brain circuits. Boyden, who worked with Deisseroth before joining the Massachusetts Institute of Technology in 2007, recounted how ideas first explored in the early 2000s evolved over the following years into a powerful set of optogenetic technologies. Today, these tools are widely used by neuroscientists and biologists to probe and manipulate complex biological systems.

2015: Recording Neural Activity with Light

While early versions of optogenetics focused primarily on stimulating neurons with light, new research from biophysicist Adam Cohen at Harvard University expanded the technology’s capabilities by enabling simultaneous stimulation and recording of neural activity. Cohen’s team developed an optical voltage indicator called QuasAr, which glows in the infrared in response to changes in cellular voltage, along with a highly blue light-sensitive channelrhodopsin. By introducing both tools into the same cells, the researchers could activate neurons with blue light while recording their electrical responses in the infrared.

“The dream is to start doing recordings in intact neural circuits to see how a single neuron takes its inputs and combines those inputs and then decides whether or not to fire,” said Cohen.

2015: Optogenetics Expands to Nonhuman Primates

That same year, systems neuroscientist Masayuki Matsumoto and colleagues at Kyoto University used optogenetics to manipulate a specific neural pathway in the brain of a macaque monkey and alter the animal’s behavior.² The researchers targeted the frontal eye field, a brain region involved in controlling eye movements. When stimulated with light, the neurons triggered rapid eye movements, demonstrating the potential of optogenetics in more complex brains and bringing the technology a step closer to clinical applications.

2017: Optogenetics Moves Toward the Clinic

In 2016, a blind woman received an injection of a genetically modified adeno-associated virus designed to deliver channelrhodopsin to retinal ganglion cells, making them responsive to light. This gave the woman rudimentary vision, and she is believed to be among the first people to receive an optogenetics-based therapy, marking a major step toward translating the technology into medicine. Beyond vision restoration, researchers have also explored optogenetic approaches for conditions such as deafness and chronic pain.

2018: Pairing Deep Brain Stimulation with Nanoparticle-Based Optogenetics

As optogenetics became widely used to study brain circuitry in organisms ranging from fruit flies to monkeys, researchers sought ways to stimulate neurons deep within the brain without invasive procedures. In 2018, scientists including postdoctoral researcher Shuo Chen and neuroscientist Thomas McHugh at the RIKEN Brain Science Institute, developed nanoparticles capable of converting tissue-penetrating near-infrared light into blue and green light emissions that could activate optogenetic proteins deep in the brain.³ Using this approach, the team successfully modified fear-related behaviors in mice by controlling neurons involved in memory formation.

2021: Blind Patient Recovers Partial Vision with Optogenetics and Engineered Goggles

Building on earlier clinical efforts, researchers reported partial vision recovery in a 58-year-old man treated with an optogenetic therapy. The team delivered a light-sensitive protein to retinal cells using an adeno-associated viral vector, then stimulated those cells using engineered goggles that projected pulses of light onto the retina. Combined with visual training, the treatment enabled the patient to detect and identify certain objects, highlighting the therapeutic potential of optogenetics in vision restoration.

2021: Optogenetics Take Home a Lasker Award

In 2021, the Albert Lasker Basic Medical Research Award was awarded to biochemist Dieter Oesterhelt of the Max Planck Institute of Biochemistry, neuroscientist Peter Hegemann of Humboldt University of Berlin, and Deisseroth for their work on light-sensitive proteins known as opsins and for advancing those discoveries into the field of optogenetics, which has transformed neuroscience research.

2024: Precision Muscle Control Through Light Signals

Optogenetics is also advancing neuroprosthetic technologies, which traditionally rely on electrical stimulation to activate muscles that no longer receive natural neural input. Researchers recently developed techniques to control genetically engineered muscles using light, enabling more precise activation than conventional electrical methods. In mouse studies, the optogenetic approach produced more consistent muscle activity patterns, potentially reducing fatigue while improving the precision and fidelity of neuroprosthetic treatments.

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