UC researchers use optogenetics to control seizures with light pulses in neurons.
Researchers at the University of California (UC)’s campuses in San Francisco, Santa Cruz, and Berkeley have recently shared a new, innovative treatment for epilepsy. By applying pulses of light to specific neurons, they’ve managed to inhibit seizure-like activity in human brain tissue obtained from epilepsy patients. This technique, known as optogenetics, involves using a harmless virus to introduce light-sensitive genes from microorganisms into targeted neurons. These genes then enable the researchers to control the activity of these neurons with light, effectively allowing them to “turn off” the neurons when seizure activity begins.
In traditional epilepsy treatment, patients whose seizures can’t be managed with medication sometimes undergo surgery to remove the brain tissue where their seizures originate. This new approach offers a less invasive alternative that may one day eliminate the need for surgery altogether. Optogenetics has been used in animal studies before, but this is the first time it has successfully demonstrated seizure control in living human brain tissue.
The UC team preserved the excised brain tissue in an environment that mimics conditions within the human skull to sustain it for several weeks of experimentation. They created a nutrient medium similar to cerebrospinal fluid, which provides the necessary nutrients to keep the neurons functioning outside the body. After setting up a system with tiny electrodes to measure neuronal electrical activity, they directed light pulses at the neurons carrying the light-sensitive proteins. This allowed them to observe how light could disrupt the abnormal electrical surges associated with seizures.
During normal brain activity, neurons communicate through low-level electrical signals, similar to casual background noise. However, during a seizure, this background noise turns into synchronized bursts of electrical activity, overwhelming brain function. The research team aimed to use light pulses to prevent or diminish these bursts by inactivating the neurons carrying the light-sensitive proteins.
To conduct their experiments, the researchers faced the challenge of minimizing physical disturbance to the brain slices, which were connected to electrodes positioned less than half the width of a human hair apart. Small shifts in tissue could have interfered with data accuracy, so the team developed a remote-controlled system that allowed them to record neuronal activity and deliver light pulses without disturbing the tissue. Using software developed by the team, the researchers were able to run the experiments remotely from Santa Cruz while the tissue remained in San Francisco.
The optogenetics approach has enabled the researchers to study the complex interactions between neurons during seizures with new clarity. They identified the types and numbers of neurons that contribute to seizure activity and determined the minimum intensity of light needed to control the neurons’ activity without causing harm.
Dr. Edward Chang, a neurosurgeon at UC San Francisco, emphasized that this new method could potentially transform epilepsy treatment. He envisions a future where patients may have access to non-invasive options for managing seizures, sparing them from the risks associated with surgery. This approach could provide patients with more precise, effective control over their condition, significantly improving quality of life.
Sources:
Pulses of light show promise in controlling seizures
Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices
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