Nav: Home

Zooming in on brain circuits allows researchers to stop seizure activity

December 16, 2019

WASHINGTON -- A team of neuroscientists at Georgetown University Medical Center have found, in animal models, that they can "switch off" epileptic seizures. The findings, published online in Proceedings of the National Academy of Sciences (PNAS), provide the first evidence that while different types of seizures start in varied areas of the brain, they all can be controlled by targeting a very small set of neurons in the brain or their tendril-like neuronal axons.

Zeroing in on specific neurons suggests that treatment for epilepsy can be improved, researchers say. For example, the deep brain stimulation used today could be minutely targeted at the cell body of these neurons or at the areas their axons touch, depending on the type of seizure, says the study's senior investigator, Patrick A. Forcelli, PhD, an assistant professor in neuroscience and in pharmacology and physiology at Georgetown.

"We have found a major choke point in epilepsy circuits in rat brains that we believe can be harnessed to disrupt the onset of seizures or to stop their propagation within the brain," he says. "Circuit-based therapy for people will help offset the known side effects that come with drug therapy and other techniques."

According to the CDC, in the U.S., about 3 million adults and almost 500,000 children have epilepsy, making the incidence about 1% of the population, and the fourth most common brain disorder. (Epilepsy is diagnosed when a person has had more than one seizure.)

Seizures occur when nerve cells in the brain misfire. While there are about 30 specific types of seizures, there are two main categories: focal, which start in particular areas of the brain, and generalized, which occur when nerve cells on both sides of the brain misfire. Within this category are tonic-clonic (formerly known as grand mal) convulsive seizure and absence (formerly known as petit mal).

Researchers have known for about 30 years that while inhibiting a certain area of the brain, the substantia nigra pars recticulata (SNpr) can help stop a seizure, the circuits by which the SNpr controls a seizure have remained unclear. The SNpr is a small area deep within the brain. "It is usually thought to be involved in movement and movement disorders," says Forcelli. "We knew targeting SNpr can stop a seizure, but we didn't know how. Neurons in this area have axonal projections that go to many different parts in the brain."

This study, he says, is built upon the pioneering work done at GUMC in the 1980s when researchers, led by Karen Gale, PhD, "built a metaphorical Rand McNally-type atlas of neuronal pathways involved in seizures and epilepsy - these maps have moved forward both basic biology and for pharmacological treatment of epilepsy." The aim of his research is "to make a "Google maps" version with higher resolution and the ability to zoom in on each address, to improve brain stimulation therapy," says Forcelli.

With his team, Forcelli used four models of experimental epilepsy in seizure-prone rats, designed to reflect a different type of seizure (absence, forebrain tonic-clonic, brainstem tonic-clonic, and limbic) seen in human epilepsies.

They were able to stop these seizures by placing light-sensitive ion channels into neurons in the SNpr; when exposed to light, the neurons can be turned on or off. They found that seizures could be turned off by either silencing activity of the SNpr cell bodies or, in some cases, the areas that these neurons project to.

"We can't target therapy if we don't know how the circuits work. Discovering that silencing one area that a SNpr projects to can turn off specific seizures suggests a much more targetable therapy. For example, deep brain stimulation could be aimed at that area," Forcelli says.

"These findings clarify a long-standing question in the field: the role these individual SNpr neural pathways play in the control of seizures," he says.
-end-
In addition to Forcelli, authors include: Evan Wicker, Veronica C. Beck, Colin Kulick-Soper, Catherine V. Kulick-Soper, Safwan K. Hyder, Carolina Campos-Rodriguez, Tahiyana Khan, and Prosper N'Gouemo.

This research was supported by grants from the Georgetown-Howard University CTSA (UL1TR000101, R01NS097762), Georgetown University Dean for Research, and the American Epilepsy Society/Epilepsy Foundation of America. Additional funding provided by the NIH (F30NS110318, R21AA027171, R01AA027660 and KL2TR001432). The authors report no other disclosures.

About Georgetown University Medical Center

Georgetown University Medical Center (GUMC) is an internationally recognized academic health and science center with a four-part mission of research, teaching, service and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter).

Georgetown University Medical Center

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.