In what might at some point turn into a brand new remedy for epilepsy, researchers at UC San Francisco, UC Santa Cruz and UC Berkeley have used pulses of sunshine to stop seizure-like exercise in neurons.
The researchers used mind tissue that had been faraway from epilepsy sufferers as a part of their remedy.
Finally, they hope the method will exchange surgical procedure to take away the mind tissue the place seizures originate, offering a much less invasive choice for sufferers whose signs can’t be managed with remedy.
The group used a way referred to as 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 dwelling human mind tissue, and it opens the door to new remedies for different neurological ailments and circumstances.
“This represents an enormous step towards a strong new method of treating epilepsy and sure different circumstances,” mentioned Tomasz Nowakowski, PhD, an assistant professor of neurological surgical procedure and a co-senior creator 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 setting that mimics circumstances 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 perfect virus to ship the genes, so they’d work within the particular neurons the group was concentrating 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 appearing usually, neurons ship alerts at totally different occasions 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 group hoped to make use of the sunshine pulses to stop the bursts by switching off neurons that contained light-sensitive proteins.
Distant-control experimentation
First, the group wanted to discover a strategy to run their experiments with out disturbing the tissue. The tiny electrodes had been solely 17 microns aside – lower than half the width of a human hair – and the smallest motion of the mind slices might skew their outcomes.
Mircea Teodorescu, PhD, an affiliate professor {of electrical} and laptop engineering at UCSC and co-senior creator of the examine, designed a remote-control system to document 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 might direct experiments from Santa Cruz on the tissue in Nowakowski’s San Francisco lab.
That method, nobody wanted to be within the room the place the tissue was being stored.
This was a really distinctive collaboration to resolve an extremely complicated analysis drawback. The truth that we really achieved this feat exhibits how a lot farther we are able to attain once we convey the strengths of our establishments collectively.”
Mircea Teodorescu, PhD, affiliate professor {of electrical} and laptop engineering at UCSC
New perception into seizures
Optogenetics permits researchers to zoom in on discrete units of neurons.
The group might see which kinds of neurons and what number of of them had been wanted to begin a seizure. And so they decided the bottom depth of sunshine wanted to alter {the electrical} exercise of the neurons in stay mind slices.
The researchers might additionally see how interactions between neurons inhibited a seizure.
Edward Chang, MD, the chair of Neurological Surgical procedure at UCSF, mentioned these insights might revolutionize look after folks with epilepsy.
“I consider that sooner or later, we cannot have to try this if we use this sort of strategy,” Chang mentioned who together with Nowakowski is a member of the UCSF Weill Institute for Neurosciences.
“We’ll have the ability to give folks way more refined, efficient management over their seizures whereas saving them from such an invasive surgical procedure.”
Supply:
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.