In what might sooner or later turn out to be 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.
Ultimately, they hope the approach will change 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.Â
The crew used a technique often called 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 illnesses and circumstances.Â
“This represents a large step towards a strong new means of treating epilepsy and certain different circumstances,” mentioned 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 spikesÂ
To maintain the tissue alive lengthy sufficient to finish the research, which took a number of weeks, the researchers created an atmosphere 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 very best virus to ship the genes, so they might work within the particular neurons the crew 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 crew hoped to make use of the sunshine pulses to stop the bursts by switching off neurons that contained light-sensitive proteins.
Distant-control experimentationÂ
First, the crew 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 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 gentle 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 means, nobody wanted to be within the room the place the tissue was being stored.Â
This was a really distinctive collaboration to resolve an extremely complicated analysis downside. The truth that we really completed this feat exhibits how a lot farther we will attain after we carry the strengths of our establishments collectively.”Â
Mircea Teodorescu, PhD, affiliate professor {of electrical} and laptop engineering at UCSCÂ
New perception into seizuresÂ
Optogenetics permits researchers to zoom in on discrete units of neurons.
The group might see which varieties 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 stay mind slices.
The researchers might additionally see how interactions between neurons inhibited a seizure.Â
Edward Chang, MD, the chair of Neurological Surgical procedure at UCSF, mentioned these insights might revolutionize look after individuals with epilepsy.
“I imagine that sooner or later, we cannot have to try this if we use this type of method,” Chang mentioned who together with Nowakowski is a member of the UCSF Weill Institute for Neurosciences.
“We’ll be capable of give individuals way 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.