On October 6, the Nobel Assembly announced that the 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell and Simon Sakaguchi for their contributions to the understanding of how immune system regulation prevents immune cells from attacking native tissues. The Nobel Prize is the highest honor in academia, with only one significant discovery or accomplishment recognized each year in each of five categories. Given the prestigious reputation of the Nobel Prize, the Assembly is tasked with choosing from numerous excellent advancements each year. Even a year before the next selection, scientists are already speculating who might win the next Nobel Prize in Physiology or Medicine. Amidst the predictions for the strongest contender for next year’s Nobel is Karl Deisseroth, Edward Boyden and Feng Zhang’s development of optogenetics.
What is Optogenetics?
The brain and nervous system are among the most complex and least understood systems within the human body. Composed of nearly 100 billion neurons which together produce human experience, emotion and thought, the brain presents an incredible challenge to researchers seeking to elucidate its inner workings. The microscopic size and sheer number of neurons, along with the intricacy of their connections, render developing a detailed and thorough understanding of brain function an extraordinarily difficult task, even with the development of advanced technologies such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). As a result, many neurological and psychiatric disorders remain poorly understood, and most available treatments focus on managing symptoms rather than addressing their underlying causes.
Emerging technologies like optogenetics, however, aim to overcome this limitation by enabling precise, circuit-level control of neural activity. Optogenetics is a remarkably specific technology, able to target and activate a singular neural circuit. Other commonly used neural stimulation techniques, such as transcranial magnetic stimulation (TMS), are specific only to the degree of centimeters, a huge area when compared to the size of human neurons, which have cell bodies of only a few dozen micrometers wide on average. With optogenetics, singular neurons or neural networks in an organism’s brain can be activated or suppressed, allowing for stunningly precise control over the living brain.
How it Works
Much as its name suggests, optogenetics combines photonics (“opto”) with genetic engineering (“genetics”). In this technique, the gene coding for a bacterial light-activated ion channel known as a channelrhodopsin is incorporated into the genetic code of specific neurons. Several methods can then be harnessed to limit channelrhodopsin expression to one specific neuron or neural pathway. Once expressed, channelrhodopsin incorporates into the cell membrane. When exposed to blue light, the channelrhodopsin opens, allowing for ion influx and triggering an action potential, which are electrical signals that allow neurons to communicate and brain activity to occur. In a similar manner, another channel protein known as halorhodopsin was isolated from archaea and hyperpolarizes a neuron in response to yellow light, thus inhibiting a neuron or circuit. In this way, neurons can be instantaneously turned on or off with light.
Above: Schematic of the workings of optogenetics in the mouse brain. Image courtesy of GEG Tech.
From the Past to the Future
The idea that neurons could be controlled with light is not a novel idea. In fact, the idea was first suggested in the 1970s by Nobel laureate Francis Crick, best known for elucidating the structure of DNA along with Rosalind Franklin and James Watson. Around the same time, work in Germany by Dieter Oesterholt and Walter Stoeckenius on algae led to the discovery of a light-sensitive channel protein. In the decades that followed, many research groups worked to devise a method to insert light-sensitive proteins into neurons, but it was not until 2005 in Karl Deisseroth’s bioengineering lab at Stanford University that a channelrhodopsin was inserted into a neuron for the first time, effectively stimulating action potentials in response to light.
Since its introduction, the optogenetic technology has been refined by research groups around the world, and the translational applications of optogenetics have been explored. For example, optogenetic stimulation of retinal cells has shown promise in partially restoring vision to patients with neurodegenerative eye diseases. Similarly, optogenetic stimulation of pancreatic cells has successfully reestablished blood glucose homeostasis in type I and type II diabetes models. Finally, its specificity makes optogenetics a strong contender for the treatment of Parkinson’s disease, where deep brain stimulation (DBS) is an effective treatment. Optogenetics can improve upon this intervention by achieving more specific stimulation of neural circuits implicated in Parkinson’s. While the applications of optogenetics have not yet been evaluated in human clinical trials, research in animal models has shown promising results for the wide range of potential applications.
Optogenetics is a rapidly advancing technology, with the potential to impact every corner of research and medicine. Considered one of the greatest advancements in modern neuroscience, the development of optogenetics has granted members of the Deisseroth lab numerous accolades and awards. Perhaps a trip to Sweden awaits them next.