From sensing light to understanding the brain: 2026 Nobel Prize in Physiology or Medicine - Daily Excelsior

Jyoti Vakhlu jyotivakhlu@jammuuniversity.ac.in Peter Hegemann, Georg Nagel and Karl Deisseroth, for their pioneering discoveries concerning light-gated ion channels and optogenetics, a miracle that will help us understand working of brain better and treat neural disorders. Every time we see an...

Peter Hegemann, Georg Nagel and Karl Deisseroth, for their pioneering discoveries concerning light-gated ion channels and optogenetics, a miracle that will help us understand working of brain better and treat neural disorders.

Every time we see an object, an extraordinary biological process is taking place inside our eyes and brain. Light reflected from an object enters the eye and reaches the retina, the light-sensitive layer at the back of the eye. But detecting light is only the beginning.The photoreceptors convert light into electrical signals. These signals are processed by networks of neurons in the retina and then transmitted through the optic nerve to the brain. In the brain, this stream of electrical information is transformed into what we experience as vision i.e the colours, shapes, movement and objects that make up our visual world. In other words, we do not see light directly. Our cells detect light, convert it into electrical signals, and our brain interprets those signals.This ability to connect light to cellular activity is one of the remarkable features of the life.

Are eyes the only organs on earth ? The answer surprisingly is , no.

A single-celled microscopic organism a green alga can detect light and respond to it. It has no eyes, no brain and no nervous system. Yet it possesses molecular machinery, that allows it to sense light in its environment.This takes us from the familiar world of human vision to a much more unexpected place the world of microorganisms.One of the organisms that became central to this story is the single-celled green alga Chlamydomonas. Scientists were curious that how does this tiny organism sense light and use that information to move towards a light source? This question attracted the attention of German scientist Peter Hegemann, formerly at the Max Planck Institute of Biochemistry, who was interested in understanding how microorganisms detect light. His work, together with that of Georg Nagel formerly at the Max Planck Institute of Biophysics, led to the identification and characterization of a remarkable light-sensitive protein called channelrhodopsin. In the early 2000s, Hegemann and Nagel showed that this protein could act as a light-gated ion channel. When activated by blue light, the channel opens and allows charged ions to pass through the cell membrane, generating an electrical response. Chlamydomonas, is s unicellular algae (a plant) and needs light for photosynthesis, the characteristic of all plants.

The importance of this discovery went far beyond understanding how an alga senses light. The researchers found that when the channelrhodopsin protein was introduced into other types of cells by transferring the gene into these cells , those cells also become sensitive to light. This was a crucial observation. It meant that light sensitivity was not restricted to the alga the molecular machinery itself could potentially be transferred to other cells. Initially this may have seemed like one more fascinating discovery in microbial biology, but researchers at Stanford turned out it to be much more than that.

From an algal protein to a neuronal switch

This is where the work of Karl Deisseroth, a neuroscientist and psychiatrist at Stanford University, became transformative. Deisseroth recognized that the light-sensitive protein discovered in algae could solve one of neuroscience's most difficult problems: how to control selected neurons with precision. Why do we want to control ( switch on and off) of the specific neuron, to directly associate it with a function. He introduced the gene encoding channelrhodopsin into nerve cells. In 2005, his group demonstrated that nerve cells containing the light-sensitive protein could be activated by blue light, producing electrical signals. Two years later, the technique was demonstrated in the brains of living mice, showing that light could be used to control neurons inside an intact brain.This was the crucial transition from microbial photobiology to modern neuroscience. Though brain helps us to see but light can not pass through to brain , hence for that tiny microscopic optic sources to illuminate the neuron's at will are also put in the brain like optical fibre. The method is known as optogenetics a combination of genetics and optics. Genetics is used to make selected neurons produce light-sensitive proteins; optics is then used to deliver light to those neurons and control their activity.A protein that had evolved in a microscopic alga had effectively become a molecular switch for neurons.

To understand the importance of this technique we need to compare how did we study and try to understand the brain and its function before optogenetics? For much of the history of neuroscience, our understanding of the brain came from observing, recording and correlating its activity. Scientists studied patients with brain injuries, examined the consequences of neurological diseases, recorded electrical activity from neurons and used technologies such as EEG, MRI and functional MRI to identify regions of the brain that become active during particular tasks. These approaches have given us an extraordinary map of the brain and helped us associate particular regions and neural circuits with functions such as movement, vision, language, memory, emotion and decision-making. But there has always been a fundamental limitation. Seeing that a group of neurons becomes active during a particular function does not necessarily tell us that those neurons cause that function. They may simply be responding to activity generated elsewhere in the brain. These methods correlated firing of neutrons with the visible function.

With optogenetics we move from correlation to causation of a function of neurons/brain.

If a particular group of neurons becomes active when we remember a face, for example, we can conclude that those neurons are associated with that process. But how can we know whether those neurons are actually necessary for the memory or whether they are simply responding to activity generated elsewhere in the brain?Traditional methods have often struggled to answer this question with sufficient precision. Electrical stimulation can activate many neighbouring neurons at once, while imaging techniques generally allow us to observe patterns of activity rather than selectively control individual populations of cells. With optogenetics researchers will be able control individual populations of cells by switch off and on particular neuron/s, this is the transition from correlation to causation.

Optogenetics offers a remarkable new way to approach this problem.By combining genetics with light, scientists gained the ability to selectively manipulate defined populations of neurons with exceptional temporal precision. Instead of merely asking:"Which neurons are active?"researchers could begin asking a much more powerful question:"What happens if we turn these neurons on -- or turn them off?"That shift from observation to precise manipulation, from correlation toward causation is one of the reasons optogenetics has had such a profound impact on neuroscience.

Researchers can now investigate neural circuits involved in memory, emotion, movement, reward, sleep and behaviour by selectively activating or inhibiting particular populations of neurons. The method has helped scientists identify circuits associated with neurological and psychiatric disorders and understand how changes in those circuits can influence behaviour.

From understanding the brain to treating disease

The implications extend beyond understanding how the brain works.One of the most exciting possibilities is whether light-controlled biology can eventually be translated into therapies. Researchers are exploring optogenetic approaches for neurological and sensory disorders, including attempts to restore vision in people with visual impairment. The principle is particularly intriguing in retinal disease: if the normal light-sensitive cells of the retina have been damaged, could other surviving cells be genetically equipped with light-sensitive proteins and made capable of responding to light again? Such approaches are being investigated clinically, but it is important to distinguish experimental therapeutic applications from established medical treatments. Significant challenges remain, including safe and precise gene delivery, long-term expression of the light-sensitive proteins, delivery of light to the appropriate cells and ensuring safety.

Nevertheless, the concept is extraordinary. A technology that began with a protein found in a microscopic alga can now allow scientists to manipulate neural activity and investigate the circuits underlying behaviour and may eventually contribute to new treatments for disorders of the nervous system.The most important lesson this story tells us is that we often cannot predict where fundamental biological research will lead. A question about how a microorganism senses its environment eventually opened a new window into one of the greatest mysteries of science i.e working of human brain.