In what might eventually become a new therapy for epilepsy, researchers from UC San Francisco, UC Santa Cruz, and UC Berkeley have utilized light pulses to inhibit seizure-like activity in neurons.
The team conducted their research using brain samples obtained from epilepsy patients during their treatment.
They aim to develop this technique into a replacement for surgical procedures that remove brain tissue where seizures begin, presenting a less invasive alternative for patients whose symptoms are not manageable through medications.
This study employed a technique called optogenetics, which uses a benign virus to introduce light-sensitive genes from microorganisms into specific neurons in the brain, making them responsive to light pulses.
This is the first time optogenetics has been demonstrated to effectively control seizure activity in living human brain tissue, paving the way for innovative treatments for other neurological disorders.
“This marks a significant advancement towards a new, effective method for treating epilepsy and potentially other conditions,” commented Tomasz Nowakowski, PhD, an assistant professor of neurological surgery and co-senior author of the study published on November 15 in Nature Neuroscience.
Controlling epilepsy’s spikes
To keep the brain tissue viable throughout the weeks-long study, the researchers replicated an environment that resembles the conditions inside the skull.
John Andrews, MD, a neurosurgery resident, positioned the tissue on a nutrient-rich medium that mirrors the cerebrospinal fluid surrounding the brain.
David Schaffer, PhD, a biomolecular engineer at UC Berkeley, identified the most effective virus for delivering the genes to the targeted neurons.
Andrews then set the tissue upon a framework of tiny electrodes capable of detecting the electrical impulses between neurons.
Under normal circumstances, neurons communicate by sending signals at various times and frequencies in a consistent, low-level activity. However, during a seizure, this activity synchronizes into intense bursts of electrical energy, overwhelming the brain’s usual communication.
The research team aimed to utilize light pulses to prevent these bursts by turning off neurons embedded with light-sensitive proteins.
Remote-controlled experimentation
Initially, the team needed a method to carry out their experiments without disturbing the tissue. The electrodes were positioned just 17 microns apart—less than half the thickness of a human hair—and even the slightest movement of the brain slices could affect their findings.
Mircea Teodorescu, PhD, an associate professor of electrical and computer engineering at UCSC and co-senior author of the study, developed a remote-control system to monitor electrical activity and send light pulses to the tissue.
Teodorescu’s lab created software that allowed the researchers to control the experiments from Santa Cruz while the tissue was housed in Nowakowski’s San Francisco lab.
This setup meant that researchers did not need to be physically present where the tissue was being studied.
“This was an exceptionally unique collaboration aimed at solving a highly complicated research issue,” said Teodorescu. “Our achievement reflects how much further we can progress by combining the strengths of our institutions.”
New understanding of seizures
Optogenetics provides researchers with the ability to focus on specific groups of neurons.
The team was able to identify which types and numbers of neurons were required to trigger a seizure and determined the least amount of light needed to alter the electrical behavior of the neurons in live brain slices.
They also observed how interactions between neurons could help suppress a seizure.
Edward Chang, MD, chair of Neurological Surgery at UCSF, stated that these findings could transform treatment for individuals with epilepsy.
“I believe that in the future, we will not have to rely on surgeries like those performed today if we adopt this type of strategy,” Chang added. “We could offer patients much finer, more effective control of their seizures, eliminating the need for invasive procedures.”
Authors: Other contributors to the study include David Shinn, Albert Wang, Matthew Keefe, PhD, Kevin Donohue, Hanh Larson, Kurtis Auguste, MD, Vikaas Sohal, MD, PhD, and Cathryn Cadwell, MD, PhD from UCSF, along with 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 from UCSC, and Lin Li and Julio Rivera-de Jesus from UC Berkeley.
Funding: This research was funded by the National Institutes of Health (grants 5R25NS070680-13, UF1MH130700, R01NS123263, R01MH120295, T32HG012344, K08NS126573, K12GM139185, and LRP0000018281), the National Science Foundation (grants 2034037, 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 contributions from the William K. Bowes Jr Foundation.
