How Light Controls Brain Cells: Karl Deisseroth Explains His Discovery

The 2026 Nobel Prize in physiology or medicine honored Karl Deisseroth , Peter Hegemann and Georg Nagel for their work developing optogenetics - a technique that allows researchers to control the activity of neurons with light.

The Conversation Weekly podcast talked to Karl Deisseroth, a neuroscientist at Stanford University, about his journey developing optogenetics and its potential to treat a wide range of neuropsychiatric conditions. What follows is an edited transcript of the podcast.

Take us back to the early 1990s. You're training to be a doctor and you start a rotation working with psychiatric patients. What questions about the brain did that raise for you?

Both basic neuroscience (people asking how the brain works) and clinical neuroscience (doctors trying to help people with brain disorders) have faced a very similar problem, which is the brain is quite mysterious and quite hard to study.

It's billions of fragile, transparent, very fast-acting cells, buried within the skull and doing very complex things. We don't have a good model for how the brain works, unlike the heart, which is very obviously a pump . We don't actually know what the brain's trying to do.

A lot of neuropsychiatric treatments are not as effective as they could be , and developing new ideas has been hard. The treatments we had were not grounded in a solid understanding of the cells involved. What are the cells actually doing? What are they trying to do? This was a problem that held back treatment.

When I was in psychiatry training in the early 2000s, and also as a medical student in the late 1990s, I was very much impressed with the magnitude of the challenge.

You went on to get a Ph.D. in neuroscience, and then you set up a lab at Stanford trying to understand how to control particular cells in the brain. What were the first experiments you did?

I have a background in molecular biology, and I knew how to work with genes. So I was motivated to see if we could use genetics to make a treatment or an intervention that targets one kind of cell.

Every cell has genes that tell it what to do. Different cells in the brain, just as other parts of the body, can be genetically targeted because different cells have different jobs. A cell that is a dopamine neuron has all the machinery needed to make the hormone dopamine. It uses different genes than a cell that makes the hormone serotonin, so they can be distinguished from each other.

And so the thought was maybe I could have a way of controlling just the dopamine cells or just the serotonin cells by inserting a specific gene into them. But I didn't know what would work well, so I tried inserting different types of genes into neurons.

Some of the genes I tried were quite conventional; they were genes from mammals that I thought might affect the activity of neurons. But one was a gene from a single-celled algae - a microbe that converts light to energy. This gene coded for a light-activated protein called channelrhodopsin-2 that Peter Hegemann and Georg Nagel identified a few years earlier.

And I thought it was worth a try. It was the least likely to work, but why not try it?

And amazingly, that was the one that worked. The genes that were lower risk didn't work, and this gene from a single-cell microbe actually did.

Walk us through what you did. You inserted the gene into rat cells, right?

I had a preparation of cultured rodent neurons in a dish - basically a 24-well plate that let me look at many different conditions at the same time in different wells of this plate. This let me test side by side the conventional mammalian genes and this gene from the algae.

So the first step was to get the genes into the cells. Then I exposed some plates of cells to light, while others I did not. I used a test to see which cells had activated.

When I looked across the cells in the screen, I found that the ones that had the algae gene and had gotten light were showing this marker of activation, whereas the others had a much lower signal. That was a really thrilling moment because it showed that this gene from a photosynthetic single-celled organism - almost as far as you can possibly be from mammals evolutionarily - was working beautifully in fragile mammalian neurons.

It was a moment of a lot of pressure and complexity, but also delight.

Listen to Karl Deisseroth on The Conversation Weekly podcast .

You went on to name your method optogenetics - the ability to control specific nerves using light in the brain - and you soon went on to using it to control living mice in various ways. What was it like in those first few years of working with live animals?

The first experiment was in 2004 , but we didn't show that it could control the behavior of freely moving mammals until 2007. So it took almost three years. But that first moment in 2007 was quite uplifting because that showed we had gone a big, big chunk of the way toward making it work.

This was an experiment that was very visible and easy to understand. The right side of the brain controls the left side of the body and attention to the left side of the world. We put in a fiber optic into the right part of a mouse motor cortex - the part that controls movement - and when we flipped the switch, the mouse immediately began going left in circles.

And then as soon as we turned off the laser light, it stopped and just looked up at us, as if nothing had happened.

That, coupled with the first experiment - those were transcendent moments.

What changed in your understanding of the brain in the moment you were able to switch particular neurons on and off?

We understood that the technique would probably work to help us understand the brain better at that moment. And then we immediately started applying it to all sorts of different cells where things were mysterious - where nobody knew or couldn't prove exactly what one cell type or another was doing in perception and cognition and action.

We were able to find cells that were involved in hunger and thirst - basic survival drives. We were able to identify cells and pathways controlling aggression and defensiveness , parenting , how all the different parts of anxiety come on together and go away together, memory , motivation .

The general applicability became clear over the subsequent years.

Researchers are now using optogenetics in attempts to restore sight in people with visual impairment. How does that work?

In 2010, two of my colleagues in Europe were interested in delivering one of these light-activated proteins to human eye samples - specifically the retina of the eye - which worked very well.

So they did careful studies in monkeys and in people. And in 2021, just five years ago, they published a paper showing they could confer light sensitivity back to the retinas of a person who was completely blind from a neurodegenerative disease called retinitis pigmentosa .

That's what we call direct optogenetics . It's somewhat complicated because you have to deliver the gene and light to the person.

And going back to your psychiatric patients, who you still see in the clinic today, how do you hope optogenetics will be able to help them?

There's a much easier and more broadly impactful avenue that we call indirect optogenetics , which uses the knowledge that comes from studying which cells matter in a symptom and then designing medications that target those cells. This is something we've really lacked in neuropsychiatry for a long time.

Indirect optogenetics is making strong headway for autism and schizophrenia . There are trials that are moving to their final stages for those disorders.

My particular clinical specialty is autism, and I see the difficulties that come with irritability and anxiety in these patients. And I can see optogenetics leading to new medications that will help.

Karl Deisseroth has received funding from the NIH and the Howard Hughes Medical Institute. He was the founder of MapLight Therapeutics, a biopharmaceutical company.