By Mengyao and henry, from QbitAI
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Just now, the 2026 Nobel Prize in Physiology or Medicine has been announced!
Karl Deisseroth, Peter HegemannandGeorg Nagelthree scientists share the award.
The Nobel Committee gave the following reason for the award: for their discoveries of light-controlled ion channels and optogenetics.
What the three laureates jointly laid the foundation for is one of the most important methodological breakthroughs in neuroscience over the past 20 years:optogenetics(Optogenetics).
Its most core breakthrough is enabling scientists to precisely activate or inhibit specific types of neurons on a millisecond timescale using light.
In the past, researchers could often only observe that a certain brain region or a certain group of neurons would become synchronously active when memory formation, emotional changes, motor control, or a certain behavior occurred.
Optogenetics changed this.
Researchers can actively manipulate the activity of specific neurons, and then observe whether the behavior subsequently occurs, weakens, or disappears, thereby advancing many questions from correlational observation to causal verification.
This method quickly became an important tool for studying neural circuits, and has been widely used in research on memory, reward, addiction, motor control, and the mechanisms of many types of neurological and psychiatric diseases.
And the starting point of this neuroscience tool revolution actually came from a single-celled green alga that swims toward light.
From the light switch in green algae to controlling neurons
The starting point of the optogenetics technical route is actually quite unexpected—green algae.
Some single-celled green algae change their swimming direction according to light. To accomplish this, they need a mechanism in their bodies that can quickly convert "light" into "electrical signals".
It is essentially a light-controlled ion channel: when light shines on it, the channel opens, ions pass through the cell membrane, and the cell membrane potential changes accordingly.
The interesting thing about applying this to neurons is that neurons transmit information by relying on ion currents and changes in membrane potential in the first place.
So as long as this "opens when it sees light" ion channel is installed into neurons, in theory one can directly use light to control when neurons fire.
What Peter Hegemann and Georg Nagel did was truly push open this door.
Hegemann has long studied how the single-celled green alga Chlamydomonas reinhardtii senses light.
This green alga has no eyes, yet can swim toward light, so Hegemann realized early on that a protein that could directly convert light stimuli into electrical signals might be hidden here.
In 2002, Hegemann, Nagel, and their collaborators identified the first Channelrhodopsin.
In 2003, they further characterized Channelrhodopsin-2, that is, ChR2, confirming that it is a cation channel that can be directly opened by light.
At this point, a "light switch" naturally existing in green algae had been found.
Next, Karl Deisseroth turned it into a true neuroscience tool.
In 2005, the Deisseroth team introduced ChR2 into mammalian neurons, and found that exposure to blue light alone was enough to induce action potentials in neurons with millisecond precision.
At this point, optogenetics truly took shape, and researchers could also use genetic methods to make only specific types of neurons express this light-sensitive protein.
So a task that was once very difficult to do suddenly became operational—
select a class of neurons, install a "light switch" on them, and then use light to precisely control when they fire and when they fall silent.
The most important thing about optogenetics is that it solved a long-standing problem in neuroscience: how to move from "seeing brain activity" to "verifying who exactly is controlling behavior."
Later, this method was widely used to study memory, sleep, reward, addiction, movement, anxiety, depression, social behavior, and brain circuits related to various neurological and psychiatric diseases.
Its biggest advantages are also clear: it can target specific cell types, offers high spatial precision, and can also achieve millisecond-level temporal control.
Over the past 20 years, researchers have continued to modify Channelrhodopsin.
Some respond faster, some can be activated by different colors of light, some are responsible for "turning on" neurons, and some for "turning off" neurons.
That is why this year's official Nobel Prize statement deliberately listed the two parts side by side: "light-gated ion channels" and "optogenetics."
The first part corresponds to the discovery and mechanistic studies of light-controlled ion channels by Hegemann, Nagel, and others.
The second part corresponds to how Deisseroth and others brought these molecular tools into the nervous system for real, and developed them into a technological system capable of manipulating neural circuits.
Stringing together the contributions of the three people actually reveals a very complete pathway——
first find the "light switch" in green algae, then install it into neurons, and finally allow scientists, for the first time, to precisely control specific cells in the brain with light.
Three scientists assembled the three most crucial puzzle pieces of optogenetics
Karl Alexander Deisseroth
Karl Alexander Deisseroth (1971-11-18 –) is an American neuroscientist, psychiatrist, and bioengineer, currently the Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University and an investigator at the Howard Hughes Medical Institute.
His career typically spans medicine, neuroscience, and engineering.
In 1992, Deisseroth graduated from Harvard University with a degree in biochemical sciences, then entered the Stanford MD-PhD program, receiving a PhD in neuroscience in 1998 and a medical doctorate in 2000.
What truly put him at the center of optogenetics was the 2005 work.
At that time, Deisseroth, together with Edward Boyden, Feng Zhang, and others, introduced Channelrhodopsin-2, that is, ChR2, into mammalian neurons, and then discovered——
that simply shining blue light could control neurons to fire action potentials with millisecond precision.
This step directly transformed the "light-gated ion channels" that had previously existed only in microorganisms into a tool that could be used to manipulate the nervous system.
Afterward, the Deisseroth team continued to advance the development of optogenetics and developed tissue clearing and imaging technologies such as CLARITY.
So his contribution is clear: he truly brought light-gated ion channels into neuroscience, making "controlling neurons with light" a method that can be used on a large scale.
Peter Hegemann｜彼得·黑格曼
Peter Hegemann (1954-12-11 –) is a German biophysicist, currently Professor of Experimental Biophysics and Hertie Professor of Neuroscience at Humboldt University of Berlin.
Compared with Deisseroth, Hegemann took a purer basic research path.
He was born in Münster, Germany, studied chemistry and biochemistry at the University of Münster and the University of Munich, and completed his doctoral research at the Max Planck Institute of Biochemistry in 1984.
From 1993, he served as a professor at the University of Regensburg, and later moved to Humboldt University of Berlin.
For decades, Hegemann has been studying a seemingly very basic question: how exactly do single-celled microalgae sense light?
This line of research later led directly to Channelrhodopsin.
Together with Georg Nagel and others, he discovered and characterized channelrhodopsins, demonstrating that this protein can integrate light sensing and the control of ion flow within a single molecule.
For optogenetics, this step was equivalent to finding the most core "component."
Without this naturally occurring light-gated ion channel, the subsequent technology of "controlling neurons with light" would have been impossible.
Georg Nagel｜格奥尔格·纳格尔
Georg Nagel, born in 1953, is a German biophysicist and currently a professor at the University of Würzburg, with long-term research on microbial photoreceptors, membrane proteins, and optogenetic tools.
Nagel was born in Weingarten, Germany, studied biology and biophysics at the University of Konstanz, and received his doctorate from the University of Frankfurt in 1988.
Afterwards, he did postdoctoral research at Yale University and Rockefeller University, and for many years led a research group at the Max Planck Institute of Biophysics.
His most crucial contributions are concentrated in the years when Channelrhodopsin's identity was truly 'nailed down'.
In 2002 and 2003, Nagel together with Hegemann and others successively identified and characterized Channelrhodopsin-1 and Channelrhodopsin-2.
Among them, ChR2 was especially critical.
They demonstrated that ChR2 itself is a cation channel that can be directly activated by light, and that after placing it into mammalian cells, illumination can cause depolarization of the cell membrane.
This step almost directly provided the later technical route: since light can alter the electrical activity of cell membranes through ChR2, installing it into neurons offers the chance to directly control neuronal firing.
Hegemann and Nagel found and figured out the 'light switch' itself, while Deisseroth truly installed this 'light switch' into neurons and developed it into optogenetics.
With these successive contributions, the entire technological system for studying the brain with light that exists today came into being.
Reference links:
[1]
https://med.stanford.edu/profiles/karl-deisseroth — profile page of Karl Deisseroth on the Stanford Medicine website
[2]
Peter Hegemann, winner of the Brain Prize 2013 for optogenetics: https://brainprize.org/winners/optogenetics-2013/peter-hegemann
[3]
https://www.biologie.hu-berlin.de/de/gruppenseiten/expbp/groupmembers/prof.-hegemann-peter — group member page for Prof. Peter Hegemann in the Experimental Biology groups at Humboldt University of Berlin