In what might sooner or later 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 stop seizure-like exercise in neurons.
The researchers used mind tissue that had been faraway from epilepsy sufferers as a part of their therapy.
Finally, they hope the approach will exchange 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 treatment.
The staff used a way often known as optogenetics, which employs a innocent virus to ship light-sensitive genes from microorganisms to a specific 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 manage seizure exercise in dwelling human mind tissue, and it opens the door to new therapies for different neurological ailments and situations.
“This represents a large step towards a strong new method of treating epilepsy and certain different situations,” stated Tomasz Nowakowski, PhD, an assistant professor of neurological surgical procedure and a co-senior writer of the research, which seems Nov. 15 in Nature Neuroscience.
Subduing epilepsy’s spikes
To maintain the tissue alive lengthy sufficient to finish the research, which took a number of weeks, the researchers created an setting 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 very best virus to ship the genes, so they might work within the particular neurons the staff 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 performing usually, neurons ship alerts at totally 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 staff 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 staff wanted to discover a solution 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 writer of the research, 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 manage 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 saved.
This was a really distinctive collaboration to unravel an extremely advanced analysis downside. The truth that we really completed this feat reveals how a lot farther we are able to attain after we carry the strengths of our establishments collectively.”
Mircea Teodorescu, PhD, affiliate professor {of electrical} and laptop engineering at UCSC
New perception into seizures
Optogenetics allows researchers to zoom in on discrete units of neurons.
The group might see which sorts of neurons and what number of of them had been wanted to start out a seizure. They usually decided the bottom depth of sunshine wanted to alter {the electrical} exercise of the neurons in dwell 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, stated these insights might revolutionize look after individuals with epilepsy.
“I consider that sooner or later, we cannot have to do this if we use this sort of method,” Chang stated who together with Nowakowski is a member of the UCSF Weill Institute for Neurosciences.
“We’ll have the ability to give individuals rather more delicate, 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.
