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

Ultimately, they hope the technique will replace surgery to remove the brain tissue causing seizures, providing a less invasive option for patients whose symptoms cannot be controlled with medication.

The team used a method known as optogenetics, which uses a harmless virus to deliver light-sensitive genes from microorganisms to a particular set of neurons in the brain. These neurons can then be activated or deactivated with light pulses.

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

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

This is the first demonstration that optogenetics can be used to control seizure 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, assistant professor of neurological surgery and co-senior author of the study, which appears November 15 in Natural neuroscience.

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

Pink and yellow reflect seizure-like activity before the light is turned on.

When the cells are illuminated, the abnormal activity dissipates.

When the light is turned off, abnormal activity resumes.

Controlling epileptic spikes

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

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

David Schaffer, PhD, a biomolecular engineer at UC Berkeley, found the best virus to deliver genes, so they 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.

Remote controlled experiment

First, the team needed to find a way to conduct their experiments without disrupting the tissues. 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 skew their results.

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

Teodorescu’s lab wrote software that allowed scientists to control the device, so the group could run experiments from Santa Cruz on tissues in Nowakowski’s lab in San Francisco.

This way no one needed to be in the room where the tissues were kept.

“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 join forces across our institutions.” »

New overview of crises

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

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

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

This information provides insight into how the approach could be used to tightly regulate the 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 the care of people with epilepsy,” said Chang, who with Nowakowski is a member of the UCSF Weill Institute for Neuroscience. “We will be able to give people much more subtle and effective control over their seizures while sparing them from such invasive surgery.”

Authors: Additional study authors: 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.

Funding: This research was supported by the National Institutes of Health (grants 5R25NS070680-13, UF1MH130700, R01NS123263, R01MH120295, T32HG012344, K08NS126573, K12GM139185, and LRP0000018281), the National Science Foundation (grants 20 34037, CNS-1730158, ACI-1540112, ACI- 1541349 and OAC-1826967), the Schmidt Futures Foundation (SF 857), Weill Neurohub grant U01NS132353, the Esther A & Joseph Klingenstein Fund, the Shurl and Kay Curci Foundation, the Sontag Foundation, and a gift from the William K. Bowes Foundation Jr.