Researchers find way to use light to turn off nerve cells in brain

Discovery gives scientists tools to study brain function

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A group of light-responsive receptors in nerve cells called kalium channelrhodopsins can effectively turn off nerve cells in the brain, offering a potential way for scientists to dissect the mechanisms underlying brain function and what goes awry in diseases like Parkinson’s, a study found.

The study, “Kalium channelrhodopsins effectively inhibit neurons,” was published in the journal Nature Communications.

Scientists, using a technique called optogenetics, can engineer nerve cells (neurons) to carry light-sensitive proteins that act as switches. The cells’ electrical activity is controlled by their response to a specific type of light, allowing scientists to assess how different cell types behave.

While optogenetics’ role in cell activation is well established, its use to inhibit a nerve cell’s responses is far less developed. Past research suggests that overactivation of the electrical activity of dopamine-producing neurons — those gradually lost throughout Parkinson’s disease — can contribute to a cell’s death.

A team led by researchers at Duke-NUS Medical School in Singapore showed that a naturally occurring group of potassium channels, known as kalium channelrhodopsins, can inhibit nerve cells’ electrical activity in different animals.

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Opening ‘tiny gates’

“These potassium channels act like tiny gates on cell membranes,” Stanislav Ott, PhD, senior research fellow at Duke-NUS and the study’s first author, said in a university press release. “When exposed to light, these gates open and let potassium ions flow through, helping to quiet the activity in the brain cells. This offers us new insights into how brain activities are regulated.”

Potassium channels are specialized proteins that sit at the surface of all human cells and control the flow of potassium ions across the cellular membrane. This flux is paramount for normal electrical activity, including the communication between nerve cells and muscles.

The light-activated kalium channelrhodopsins allow potassium ions to leave a neuron, causing changes in their electrical activity across the membrane. This process, called hyperpolarization, impairs the nerve cell’s ability to generate an action potential firing, or the ability to stimulate an electrical signal. Without it, the communication of neurons and other cells is greatly suppressed or even silenced.

“We’ve developed other remote-control switches previously, but we’ve found these potassium channels to be even more versatile, providing a very useful way to study how the brain works,” said Adam Claridge-Chang, PhD, associate professor at Duke-NUS and the study’s lead author.

The researchers tested and confirmed the inhibitory activity of the kalium channelrhodopsins in three animal models, the fruit fly Drosophila, the worm Caenorhabditis elegans, and zebrafish.

The ability to use light-triggered potassium channels to silence the activity of nerve cells opens new strategies to study the interactions between different brain regions in healthy but also diseases states, like Parkinson’s, the researchers said.

“Unlocking the mysteries of the brain remains one of science’s greatest challenges,” Patrick Tan, PhD, senior vice-dean for research at Duke-NUS. “Research like this by Adam Claridge-Chang and team equips scientists with better tools to study the intricate communication that goes on in the human brain and is essential to advancing our understanding of both healthy brains and neurological disorders, understanding that will enable us to develop effective new treatments for these conditions.”