Anyone who has stood in front of an unlabeled breaker box knows the routine.
You flip the switches one by one while someone in the next room shouts which lights just went dark. For much of neuroscience’s history, scientists had no equivalent breaker box for the brain. To understand what a region did, researchers studied the effects of injuries or created small areas of damage, called lesions, in animal models to observe what changed.
One of the most famous cases occurred in 1848, when an iron rod passed through the head of railroad worker Phineas Gage. The rod entered his left cheek, passed through the front of his brain and exited through the top of his skull.
Gage survived, but people who knew him reported changes in his personality and behavior. His case became one of the most widely studied in neuroscience and helped researchers understand the role of the frontal cortex.
Still, injuries and lesions can affect entire regions of the brain, making it difficult to determine the functions of specific groups of neurons.
A discovery recognized with this year’s Nobel Prize in Physiology or Medicine helped change that. Now, two laboratories at East Tennessee State University are using the technology to study the brain’s circuits, one group of neurons at a time.
On Oct. 5, the Nobel Assembly at the Karolinska Institutet awarded the 2026 Nobel Prize in Physiology or Medicine to Karl Deisseroth, a professor at Stanford University, and German biophysicists Peter Hegemann of Humboldt University of Berlin and Georg Nagel of the University of Würzburg.
The three were recognized for their discoveries involving light-gated ion channels and optogenetics, a technique that allows scientists to control the activity of specific cells using light.
The technology traces its origins to Chlamydomonas, a single-celled green alga that moves toward sunlight.
Hegemann and Nagel helped identify proteins called channelrhodopsins, which respond to light by opening channels in cell membranes. In 2005, Deisseroth’s laboratory demonstrated how these light-sensitive proteins could be used to activate neurons with flashes of blue light.
The research helped establish optogenetics as a tool for studying brain activity.
Scientists can use modified viruses to introduce genes for light-sensitive proteins into selected neurons. By delivering light through thin optical fibers, researchers can activate or inhibit specific cell populations and study their roles in brain function.
At ETSU’s Quillen College of Medicine, researchers are already using related techniques to investigate memory and the effects of trauma.
The East Tennessean previously profiled Tatiana Viena, an assistant professor in the Department of Biomedical Sciences whose laboratory studies the nucleus reuniens, a region of the thalamus involved in communication between areas of the brain associated with memory and decision-making.
Using custom 3D-printed devices that combine electrodes and fiber optics, her team studies how activating or inhibiting specific neurons affects brain activity and memory-related processes.
“We can activate or inactivate,” Viena said. “We look at both gain of function and loss of function.”
The East Tennessean also profiled the laboratory of Justin Gass, where postdoctoral fellow Liza Wills studies neurons involved in fear extinction, the process through which the brain learns that a previously threatening situation is no longer dangerous.
Wills uses techniques that allow researchers to identify neurons activated during learning and examine how stress and alcohol exposure affect those cells.
“I’ve found that when you combine stress and alcohol exposure, it damages the specific brain-cell populations responsible for helping the brain encode fear extinction,” Wills said.
Both laboratories are working to answer a question that was difficult to investigate with earlier methods: What does a specific group of neurons actually do?
Optogenetics is also being investigated for potential clinical applications.
In 2021, researchers led by José-Alain Sahel reported in the journal Nature Medicine that a man with retinitis pigmentosa, an inherited eye disease that causes progressive vision loss, regained some ability to identify objects after receiving an experimental optogenetic treatment.
The treatment involved introducing light-sensitive proteins into retinal cells and using specialized goggles to deliver visual information.
Other researchers are investigating optogenetic approaches to restoring vision and developing light-based cochlear implants that could stimulate auditory pathways more precisely than conventional electrical devices.
From a single-celled alga responding to sunlight to experiments investigating vision restoration, optogenetics has changed how scientists study the nervous system.
In Johnson City, ETSU researchers are using the technology to examine how individual groups of neurons contribute to memory, learning and the effects of neurological disorders.
