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Controlling the brain with light earns a physiology Nobel
The entire field of optogenetics traces back to light-seeking algae.
Over decades of research, scientists have built up a partial picture of what specialized cells within the brain and spinal cord do. By studying how the brain develops, they could identify genes that were active in different populations of neurons and where in the brain those neurons resided. In some cases, these genes could then be used to genetically delete the neurons, allowing us to get some indication of what they might be doing, building on the information we’ve obtained from studies of brains with damaged regions.
But this approach has its limits. The brain is flexible enough to potentially adapt to the loss of some cells, and their loss early in development may alter the development of any neurons they would have normally formed connections with. It would be far more informative to activate and shut down the neurons in an otherwise intact brain.
Today’s Nobel Prize in Physiology or Medicine rewards three people—Karl Deisseroth, Peter Hegemann and Georg Nagel—who developed our ability to do precisely that. Starting from studies of single-celled algae that are attracted to light, these and many other researchers built an entire field of study that we now call optogenetics: using light to alter the behavior of nerve cells marked by the activity of individual genes.
Nerve impulses are generated by proteins called ion channels, which sit in the membrane and allow charged atoms to cross it. The nervous system uses a population of ion channels that are only active under specific circumstances, like when they sense a neurotransmitter or experience voltage changes. It’s this fine level of control that allows specialized nerve cells to send impulses only under specific circumstances, keeping the brain from descending into a haze of electrical noise.
So if we want to find out what any of the multitudes of specialized nerve cells might be doing, the easiest way is to hijack this system: force the cell to send ion-based impulses when we tell it to, and see how the animal’s behavior changes.
The Nobel Committee notes that this idea was obvious enough that people tried several methods of doing so before developing optogenetics. But it turns out “the easiest way” did not mean “easy,” and most of these methods didn’t end up widely used because they involved some combination of needing to insert multiple genes, supplying the nerve cells with some very specific chemicals, or using lasers at an intensity that physically damaged the cells.
The ultimate solution, it turned out, was lurking in a single-celled algae called Chlamydomonas. The organism’s single cell is remarkably complicated, having two flagella that help it move around, and an eye spot that detects the light it moves toward. People had been studying the organism for quite some time as a model for basic biological processes.
This is where Hegemann, then working at Berlin’s Humboldt University, entered the picture. He and his coworkers managed to hook an electrode up to a Chlamydomonas and showed that exposing it to a flash of light resulted in a very rapid influx of ions, suggesting the light was triggering an ion channel to open. As other scientists started scanning the messenger RNAs made by Chlamydomonas, Hegemann spotted a couple of genes that were similar to a light-activated ion pump found in an archaeal species.
Suspecting these might be responsible for the ion fluxes in Chlamydomonas, Hegemann used RNA interference to block their activity. This did limit the flow of ions in response to light, clearly implicating these genes in the organism’s light sensing.