In what may at some point turn into a brand new therapy for epilepsy, researchers at UC San Francisco, UC Santa Cruz and UC Berkeley have used pulses of sunshine to forestall seizure-like exercise in neurons.
The researchers used mind tissue that had been faraway from epilepsy sufferers as a part of their therapy.
Ultimately, they hope the approach will substitute surgical procedure to take away the mind tissue the place seizures originate, offering a much less invasive possibility for sufferers whose signs can’t be managed with medicine.
The workforce used a way often called optogenetics, which employs a innocent virus to ship light-sensitive genes from microorganisms to a selected set of neurons within the mind that may be switched on and off with pulses of sunshine.
It’s the first demonstration that optogenetics can be utilized to regulate seizure exercise in residing human mind tissue, and it opens the door to new therapies for different neurological illnesses and situations.
“This represents a large step towards a strong new approach of treating epilepsy and sure different situations,” stated Tomasz Nowakowski, PhD, an assistant professor of neurological surgical procedure and a co-senior writer of the examine, which seems Nov. 15 in Nature Neuroscience.
Subduing epilepsy’s spikes
To maintain the tissue alive lengthy sufficient to finish the examine, which took a number of weeks, the researchers created an surroundings that mimics situations contained in the cranium.
John Andrews, MD, a resident in neurosurgery, positioned the tissue on a nutrient medium that resembles the cerebrospinal fluid that bathes the mind.
David Schaffer, PhD, a biomolecular engineer at UC Berkeley discovered the most effective virus to ship the genes, so they might work within the particular neurons the workforce was focusing on.
Andrews then positioned the tissue on a mattress of electrodes sufficiently small to detect {the electrical} discharges of neurons speaking with one another.
When the mind is performing usually, neurons ship indicators at completely different instances and frequencies in a predictable, low-level chatter. However throughout a seizure, the chatter synchronizes into loud bursts {of electrical} exercise that overwhelm the mind’s informal dialog.
The workforce hoped to make use of the sunshine pulses to forestall the bursts by switching off neurons that contained light-sensitive proteins.
Distant-control experimentation
First, the workforce wanted to discover a solution to run their experiments with out disturbing the tissue. The tiny electrodes have been solely 17 microns aside – lower than half the width of a human hair – and the smallest motion of the mind slices may skew their outcomes.
Mircea Teodorescu, PhD, an affiliate professor {of electrical} and pc engineering at UCSC and co-senior writer of the examine, designed a remote-control system to file the neurons’ electrical exercise and ship mild pulses to the tissue.
Teodorescu’s lab wrote software program that enabled the scientists to regulate the equipment, so the group may direct experiments from Santa Cruz on the tissue in Nowakowski’s San Francisco lab.
That approach, nobody wanted to be within the room the place the tissue was being saved.
This was a really distinctive collaboration to unravel an extremely advanced analysis drawback. The truth that we really achieved this feat exhibits how a lot farther we are able to attain after we deliver the strengths of our establishments collectively.”
Mircea Teodorescu, PhD, affiliate professor {of electrical} and pc engineering at UCSC
New perception into seizures
Optogenetics allows researchers to zoom in on discrete units of neurons.
The group may see which forms of neurons and what number of of them have been wanted to begin a seizure. And so they decided the bottom depth of sunshine wanted to vary {the electrical} exercise of the neurons in reside mind slices.
The researchers may additionally see how interactions between neurons inhibited a seizure.
Edward Chang, MD, the chair of Neurological Surgical procedure at UCSF, stated these insights may revolutionize look after individuals with epilepsy.
“I imagine that sooner or later, we can’t have to do this if we use this type of strategy,” Chang stated who together with Nowakowski is a member of the UCSF Weill Institute for Neurosciences.
“We’ll have the ability to give individuals far more refined, efficient management over their seizures whereas saving them from such an invasive surgical procedure.”
Supply:
College of California – San Francisco
Journal reference:
Andrews, J. P., et al. (2024). Multimodal analysis of community exercise and optogenetic interventions in human hippocampal slices. Nature Neuroscience. doi.org/10.1038/s41593-024-01782-5.
