In what could one day become a new treatment for epilepsy, researchers at UC San Francisco, UC Santa Cruz and UC Berkeley used pulses of light to prevent seizure-like activity in neurons.
The researchers used brain tissue removed from epilepsy patients as part of their treatment.
Ultimately, they hope the technique will replace surgery to remove the brain tissue where seizures originate, 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 transfer light-sensitive genes from microorganisms to a specific set of neurons in the brain that can be turned on and off by pulses of light.
It is the first evidence that optogenetics can be used to control epileptic activity in living human brain tissue and opens the door to new treatments for other neurological diseases and conditions.
“This represents a huge step toward a powerful new way to treat epilepsy and potentially other conditions,” said Tomasz Nowakowski, PhD, assistant professor of neurological surgery and co-senior author of the study, which appears Nov. 15 in Nature Neuroscience.
Fighting epilepsy spikes
To keep the tissue alive long enough to complete the study, which took several weeks, the researchers created an environment that mimics the conditions inside the skull.
Neurosurgery resident John Andrews, MD, placed the tissue in 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 on the specific neurons the team was targeting.
Andrews then placed the tissue in a layer of electrodes small enough to detect the electrical discharges of neurons communicating with each other.
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 loud bursts of electrical activity that overwhelm the brain’s casual chatter.
The team hoped to use the light pulses to prevent the bursts by turning off neurons that contained light-sensitive proteins.
Experiment with remote control
First, the team had to find a way to perform 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 parts of the brain could alter their results.
Mircea Teodorescu, PhD, 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 pulses of light to the tissue.
Teodorescu’s lab wrote software that allowed scientists to control the device, so the team could run experiments from Santa Cruz on the web to Nowakowski’s lab in San Francisco.
That way, no one needed to be in the room where the tissue was kept.
This was a very unique collaboration to solve an incredibly complex research problem. The fact that we actually achieved this feat shows how far we can go when we combine the strengths of our institutions.”
Mircea Teodorescu, PhD, associate professor of electrical and computer engineering at UCSC
New insight into seizures
Optogenetics allows researchers to zoom in on discrete sets of neurons.
The team could see which types of neurons and how many of them were needed to initiate a seizure. And they determined the lowest light intensity needed to change the electrical activity of neurons in live brain slices.
The researchers could also see how interactions between neurons inhibited a seizure.
Edward Chang, MD, chairman of Neurological Surgery at UCSF, said these ideas could revolutionize the care of people with epilepsy.
“I think in the future, we won’t have to do that if we use this kind of approach,” said Chang, who along with Nowakowski is a member of the UCSF Weill Institute for Neurosciences.
“We’ll be able to give people much more subtle, effective control of their seizures while saving them from such an invasive surgery.”
Source:
Journal Reference:
Andrews, JP, et al. (2024). Multimodal assessment of network activity and optogenetic interventions in human hippocampal slices. Nature Neuroscience. doi.org/10.1038/s41593-024-01782-5.
