The discovery sheds light on the brain’s mysteries: “There is a before and an after”

“There was no way to test what would happen to a behaviour if I activated a particular type of nerve cell or if I stopped the activity of that type of nerve cell?” Optogenetics made exactly that possible: to switch the activity of specific nerve cells on or off and observe how the behaviour changed,” says Konstantinos Meletis , professor at the Department of Neuroscience, Karolinska Institutet, who has collaborated with Karl Deisseroth.

The researchers could therefore move from correlation to causality: from observing that a nerve cell is active when a certain behaviour occurs to testing whether the activity in the nerve cell actually causes the behaviour.

“It is so incredibly fundamental, so crucial to brain research. You can divide the history of neuroscience into a ‘before’ and an ‘after’ this discovery. Optogenetics has completely transformed what is possible to do,” says Konstantinos Meletis.

From algae to nerve cells

The story behind this year’s Nobel Prize began in the early 1990s, when the German researcher Peter Hegemann became interested in how the single-celled alga chlamydomonas can detect and swim towards light.

Together with fellow Nobel laureate, George Nagel, also from Germany, he succeeded in identifying a light-sensitive type of protein in the alga during the 2000s. The protein was named channelrhodopsin.

They discovered that when blue light struck the protein, a channel in the cell membrane opened. Electrically charged particles, known as ions, could then flow into the cell and generate an electrical signal. A key finding was that the the same protein and mechanism could also function in other types of cells.

From there came the next major idea.

The American researcher Karl Deisseroth realised that the protein channelrhodopsin could be used to control nerve cells.

The researchers introduced the gene coding for the protein channelrhodopsin into nerve cells grown in a laboratory, leading to formation of the light-sensitive protein on the surface of the nerve cells. When the nerve cells were exposed to blue light, the ion channels opened and the nerve cells began to generate and transmit electrical signals, just as nerve cells naturally do in the brain.

In effect, they had created a light-controlled switch for nerve cells.

Two years later, Karl Deisseroth and his colleagues were able to use the technique to control nerve cells in the brains of living mice.

Since then, optogenetics has become a central tool in neuroscience. By controlling specific nerve cells, researchers can investigate how different brain circuits influence movement, memory, emotions and behaviour.

The technique is also being explored as a potential foundation for future treatments.

“The technology is already being used in attempts to restore vision in people who are blind. The hope is that it will also become a tool for treating neurological disorders such as Parkinson’s disease and Alzheimer’s disease, as well as psychiatric disorders such as depression, anxiety and PTSD,” says Konstantinos Meletis.

A collaboration that spread across the globe

Around 2008, Konstantinos Meletis was a postdoctoral researcher at MIT in the United States alongside Marie Carlén , now a professor at the Department of Neuroscience , Karolinska Institutet. There, they collaborated with Karl Deisseroth’s laboratory at Stanford University. This marked the beginning of a long-standing scientific collaboration. Deisseroth was invited to Karolinska Institutet on several occasions and held an affiliated research position between 2013 and 2019.

“Karl is an absolutely exceptional scientist and human being. In addition to being incredibly intelligent, he is remarkably generous. This has contributed to the breakthrough in optogenetics,” says Marie Carlén, and continues:

“As soon as he set up his lab and carried out the first optogenetics studies in the mid-2000s, he began sharing these tools with others. Since then, they have spread to thousands of laboratories around the world. I would say that is quite unique. It has enabled laboratories everywhere to continue expanding our knowledge of the brain.”

For Konstantinos Meletis, this year’s Nobel Prize is a reminder of the value of basic research and the importance of investing in work whose future significance is not yet known.

“We must be willing to trust the unexpected, to trust major discoveries that arise from things we did not anticipate. Optogenetics did not emerge because someone decided we needed a method to cure a specific disease. It developed frompeople who were deeply committed to a fundamental scientific question. Only later could its potential be recognised,” he says.

He points to Hegemann’s and Nagel’s early research on light-sensitive proteins in algae as an example. At the time, it was far from obvious how important the discovery would become for neuroscience.

“What funding body would choose to support research on algae in order to discover this protein? And yet, 20 years later, it has transformed the entire field of neuroscience. That is what makes it so inspiring.”