In what could one day be a new treatment for epilepsy, researchers at UC San Francisco, UC Santa Cruz and UC Berkeley have used pulses of light to prevent seizure-like activity in neurons in brain tissue taken from epilepsy patients as part of their treatment.

Eventually, they hope the technology will replace surgery to remove the brain tissue where seizures occur, providing a less invasive option for patients whose symptoms cannot be controlled with medication.

The team used a method called optogenetics, which uses a harmless virus to deliver light-sensitive genes from microorganisms to a specific set of neurons in the brain. These neurons can then be turned on or off with pulses of light.

When the brain is acting normally, neurons send signals at different times and frequencies in a predictable low-level chatter. But during a seizure, the chatter synchronizes into loud bursts of electrical activity that overwhelm the brain’s casual conversation.

The team used the light pulses to prevent bursts by turning off neurons that contained light-sensitive proteins.

It is the first demonstration that optogenetics can be used to control seizure-like activity in living human brain tissue, and it opens the door to new treatments for other neurological diseases and conditions.

“This represents a giant step toward a powerful new way to treat epilepsy and likely other conditions,” said Tomasz NowakowskiPhD, an assistant professor of neurological surgery and a co-senior author of the study, which appears Nov. 15 in Nature’s Neuroscience.

These images show how seizure-like activity can be dampened by pulses of light in a piece of living brain tissue containing light-sensitive proteins.

The pink and yellow reflect seizure-like activity before the light comes on.

When the cells are illuminated, the abnormal activity disappears.

When the lights go out, abnormal activity starts again.

Attenuate epileptic spikes

To keep the surgically removed tissue alive long enough to complete the study, which took several weeks, the researchers created an environment that mimics the conditions inside the skull.

John AndrewsMD, neurosurgery resident, placed the tissue on a nutrient medium similar to the cerebrospinal fluid that bathes the brain.

David Schaffer, PhD, a biomolecular engineer at UC Berkeley found the best virus to deliver the genes so they would work in the specific neurons the team was targeting.

Andrews then placed the tissue on a bed of electrodes small enough to detect electrical discharges from neurons communicating with each other.

Experiment with remote control

First, the team needed to find a way to run their experiments without disturbing the tissue. The tiny electrodes were only 17 microns apart—less than half the width of a human hair—and the slightest movement of the brain slices could distort their results.

Mircea TeodorescuPhD, an associate professor of electrical and computer engineering at UCSC and co-author of the study, designed a remote control system to record the neurons’ electrical activity and deliver light pulses to the tissue.

Teodorescu’s lab wrote software that allowed the researchers to control the apparatus, allowing the group to direct experiments from Santa Cruz on the tissue in Nowakowski’s lab in San Francisco.

That way, no one needed to be in the room where the tissue was stored.

“This was a very unique collaboration to solve an incredibly complex research problem,” Teodorescu said. “The fact that we actually accomplished this feat shows how much further we can go when we bring together the strengths of our institutions.”

New insight into seizures

We will be able to give people much more subtle, effective control over their seizures while saving them from such invasive surgery.”

The technique allowed the team to see that they could stop the seizure-like activity by stimulating a surprisingly small number of neurons as well as determine the lowest light intensity needed to change the electrical activity.

They were also able to observe how neurons interact while inhibiting a seizure.

These insights provide a deeper understanding of how the approach can be used to tightly regulate brain activity that leads to seizures and could spare patients the invasiveness and side effects of removing brain tissue, said Edward ChangMD, Chair of Neurological Surgery at UCSF.

“This type of approach could really improve care for people with epilepsy,” said Chang, who, along with Nowakowski, is a member of the UCSF Weill Institute for Neurosciences. “We will be able to give people much more subtle, effective control over their seizures while saving them from such an invasive surgery.”

Author: Additional authors on the study: David Shinn, Albert Wang, Matthew Keefe, PhD, Kevin Donohue, Hanh Larson, Kurtis Auguste, MD, Vikaas Sohal, MD, PhD, and Cathryn Cadwell, MD, PhD of UCSF, Jinghui Geng, Kateryna Voitiuk, Matthew Elliott, Ash Robbins, Alex Spaeth, Daniel Solis, Jessica Sevetson, PhD, Drew Ehrlich, Sofie Salama, PhD, Tal Sharf, PhD, and David Haussler, PhD, of UCSC, and Lin Li and Julio Rivera-de Jesus from UC Berkeley.

Financing: This research was supported by the National Institutes of Health (grants 5R25NS070680-13, UF1MH130700, R01NS123263, R01MH120295, T32HG012344, K08NS126573, K12GM013918, National Science Foundation and L805013918). L805013918). (grants 2034037, CNS-1730158, ACI-1540112, ACI-1541349 and OAC-1826967), Schmidt Futures Foundation (SF 857), Weill Neurohub grant U01NS132353, Esther Kay Shurlingen Foundation and Joseph Kyllingen Foundation, Joseph Kyllingen Sontag Foundation, and a gift from William K. Bowes Jr. Foundation.