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Shining a light on the brain: optogenetics and epilepsy

An estimated 3 million Americans have epilepsy, but most of the fundamental questions about the condition have yet to be answered.

“It’s a really diverse disorder with many different types,” said Esther Krook-Magnuson, Ph.D., assistant professor in the Department of Neuroscience of the Medical School and MnDRIVE neuromodulation faculty scholar. She studies epilepsy in mice, specifically epilepsy affecting the temporal lobe.

Epilepsy manifests itself through seizures. Some may lead to convulsions, while others, like those in absence epilepsy, are non-convulsive and result in a lack of response or a staring-off-into-space effect. But for the most part, why and how epilepsy works remains a mystery.

“That can be very frustrating for patients,” Krook-Magnuson said.

In fact, up to 40 percent of patients don’t achieve seizure control with traditional treatment using medication. Some seek surgical options, like removal of “bad” brain tissue. But that isn’t an option for all patients, including those with bilateral temporal lobe epilepsy, because multiple parts of the brain — including vital portions which work with memory development — contribute to the seizures.

So Krook-Magnuson took a targeted approach using a technique called optogenetics, which uses light to alter brain activity. Software connected to the brain picks up when a seizure happens, and the software triggers light delivery.

Optogenetics takes targeted interventions a step further than other treatments. Not only can scientists detect the seizure area, but they can also target specific cell groups and adjust activity within those cells.

To do this, scientists inject certain proteins to sensitize parts of the brain to light. Depending on the cells and the regions of the brain that are being altered, scientists may be able to cause seizures, worsen ongoing seizures or stop seizures.

“Ideally, we hope to develop a way to target just the cells causing the seizure, selectively inhibiting them or disconnecting them from the rest of the network,” she said.

Her work will help scientists and physicians to better understand brain circuits and how to stop seizures. If translated for use in humans, it could allow physicians to develop specialized treatment plans catered to each individual’s case of epilepsy.

Optogenetics is a fairly new field, only picking up steam in the last five to ten years. It was named “Method of the Year” by Nature Methods in 2010.

“Optogenetics is the tool we’ve been waiting for,” Krook-Magnuson said. “Now we’re asking questions we couldn’t even ask before. The brain is very complex, and we finally have the tools to get some answers.”

Krook-Magnuson’s work researching optogenetics and epilepsy is supported by NIH grant funding and MnDRIVE, a legislative investment in UMN research focusing on brain conditions, robotics, the environment and global food.

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