“Optogenetics has changed the way we study the brain”
This year’s Nobel Prize in Physiology or Medicine honors the development of optogenetics. At the University of Gothenburg, Linda Engström Ruud uses the technique to understand how drugs such as semaglutide affect the brain, appetite, and body weight.
“Optogenetics has changed the way we study the brain. We can make specific neurons sensitive to light and then switch them on or off. This allows us to investigate the role of those particular cells and begin to understand causal relationships in the brain,” says Linda Engström Ruud, Associate Professor of Physiology at Sahlgrenska Academy, University of Gothenburg.
This year’s Nobel Prize is awarded to Karl Deisseroth, Peter Hegemann, and Georg Nagel for discoveries that led to the development of optogenetics. The technique uses light-sensitive proteins to control the activity of selected neurons with great precision.
A research tool
In the type of optogenetic experiments conducted by Linda Engström Ruud’s group, researchers need to insert a thin optical fiber into the brain to deliver light to the neurons. The technique is therefore invasive and is used primarily as a research tool in animal models.
Optogenetics has opened up entirely new possibilities in neuroscience. Researchers can, for example, activate a specific group of neurons or particular pathways originating from those neurons and observe whether behavior changes. This allows them to investigate causal relationships and gain a better understanding of what different neurons actually do.
“It is an incredibly exciting method and has been hugely important for how we study brain function,” says Linda Engström Ruud.
Drug effects
Engström Ruud’s research group uses optogenetics, among other methods, to understand how GLP-1 receptor agonists, including semaglutide, affect the brain. These drugs are used to treat type 2 diabetes and obesity and can produce substantial weight loss, in part by reducing appetite. But researchers still do not fully understand which neurons and neural circuits in the brain are responsible for the drugs’ various effects.
In experiments in mice, the researchers can identify neurons that respond to semaglutide and then use optogenetics to activate or inhibit specific neurons and their connections to other parts of the brain. They can then study, for example, how this affects the mice’s food intake and body weight.
“We can trace where neurons send their projections and then manipulate activity in these neural pathways. This allows us to investigate what happens to food intake and body weight, for example. It gives us an opportunity to understand what different parts of these neural networks actually do,” says Linda Engström Ruud.
A revolutionary technique
In a study published in Cell Metabolism last year, the research group identified a population of neurons in the brainstem that is necessary for semaglutide to cause weight loss.
The researchers are now taking the next step, using optogenetics to understand how these neurons drive this effect. By using light to stimulate different neural pathways originating from the cells, they can study how the mice’s food intake, metabolism, and body weight are affected.
“It is such an important and revolutionary technique. It has enabled us to ask questions about brain function that were previously very difficult to answer,” says Linda Engström Ruud.
