The human brain is an amazing machine powered by electricity. Carefully controlled patterns of changing electrical charges in neurons allow us to to think, move, and speak. When this system is disrupted, very bad things happen. A seizure occurs when a sudden surge of electrical activity in the brain interrupts normal functioning. Seizures are accompanied by various symptoms, including everything from unusual thoughts and uncontrollable movements to a total loss of consciousness. Sometimes seizures have a known cause—a brain injury or drug withdrawal, for example. But often what happens in the brain to cause a seizure is not obvious. Epilepsy is a disease characterized by repeated, unprovoked seizures, and it is a complex condition caused by an intertwining set of genetic and environmental factors. In a recent study published in G3, Arunesh Saras and Mark A. Tanouye untangle a new connection between genetics and temperature in a fruit fly model. They show that even a brief hot shock suppresses seizures in a set of mutants with epilepsy-like phenotypes.

Animal models of complex diseases like epilepsy are crucial because they can be  manipulated in the lab and provide a known, controllable genetic background for experimentation. Bang-sensitive Drosophila melanogaster mutants are used as a model system to study seizure disorders. Their name comes from the fact that a mechanical shock or high frequency electrical stimulation easily induces seizure-like activity, including behaviors like paralysis. This trait can be caused by multiple genotypes and some are more sensitive to seizures than others.

In this study, Saras and Tanouye tested the effects of heat shock on bang-sensitive mutants. Surprisingly, they found that even a short exposure to high temperatures suppressed seizures in several different bang-sensitive mutants. After just 30 seconds of heat shock at 38ºC, seizures could not be induced in even the most sensitive mutants genotypes. Unfortunately, this effect doesn’t last long: all of the mutant flies returned to having inducible seizures within an hour. For some genotypes, the effect of heat shock only lasted for around two minutes. The authors used precise electrophysiology recording to confirm that heat shock raised the minimum voltage of electrical stimulation required to induce a seizure in these flies.  

Like in epilepsy, the seizures in these experiments are the result of an interaction between genetics and the environment. In fact, the authors initially expected the stress caused by heat shock to make bang-sensitive mutants more susceptible to seizures. But since the exact opposite turned out to be the case, they began investigating possible mechanisms for temperature-dependent seizure suppression. They chose a set of genes already known to be involved in thermoregulation or neuronal activity in D. melanogaster and used RNAi to knockdown their expression in bang-sensitive mutants. None of them had an effect on seizure suppression except for the gene rutabaga (rut), a key enzyme in the cAMP signalling pathway.

The signaling molecule cAMP is an important component of many different physiological processes, including temperature preference behavior in flies. When rut expression was knocked down and cAMP levels decreased, bang-sensitive mutants became susceptible to seizures again even after heat shock. This result was confirmed using a bang-sensitive mutant with a rut knock-out mutation, and electrophysiology recording showed that after heat shock the bang-sensitive rut double mutants required a significantly lower amount of electrical stimulation to trigger a seizure.  

These results suggest the protective effect of high temperature works by raising the threshold of electrical activity required to trigger a seizure, and this process is dependent on high levels of cAMP. Though it is still unclear exactly how cAMP interacts with the neuronal processes responsible for seizures, knowing it is involved opens up many new avenues of study. Figuring out how seizures are triggered or suppressed in fruit flies may lead to answers for the millions of humans who struggle with epilepsy.     

Saras, A., & Tanouye, M. A. (2016). Seizure Suppression by High Temperature via cAMP Modulation in Drosophila. G3: Genes|Genomes|Genetics, 6(10), 3381-3387. DOI:10.1534/g3.116.034629

http://www.g3journal.org/content/6/10/3381.full

, , ,

Katie is a science writer at GSA. She did her PhD work on the evolutionary consequences of genetic conflict in fruit flies at the University of Georgia.

View all posts by Katie Pieper »

Read more in

  • Early Career Leadership Spotlight: Julio Molina Pineda 

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Julio Molina Pineda  Policy and Advocacy University of Arkansas Research Interest  My research interests focus on using model organisms to genetically dissect complex traits related to human disease. My…

  • Peiwei Chen

    Early Career Leadership Spotlight: Peiwei Chen

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Peiwei Chen Accessibility Subcommittee California Institute of Technology Research Interest Far from a harmonious place, the genome is a battleground, where every bit of DNA fights for inheritance and…

  • #Dros23 GSA Poster Award winners

    We are pleased to announce the GSA Poster Award winners from the 64th Annual Drosophila Research Conference! Undergraduate and graduate student members of the GSA were eligible for the awards, and a hard-working team of postdocs volunteered their time as judges. Congratulations to all! Undergraduate Students 1st Place: Sofia Karter Lopez, University of Toronto “Rab11 mediates E-cadherin recycling during…

  • Congratulations to the Fall 2022 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Fall 2022! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • GENETICS & G3 editors

    New editors join GENETICS, G3 editorial boards

    Several new editors are joining the GSA Journals. We’re excited to welcome Ricardo Zayas to the GENETICS editorial board under the Molecular Genetics of Development section, and on the G3: Genes|Genomes|Genetics board, we welcome Polly Campbell, Kevin Vogel, Joe Parker, and Ricardo Mallarino. Ricardo Zayas Associate Editor Ricardo Zayas is a Professor of Biology at…

  • Worms and Flies Provide Key Clues to Medical Mystery

    This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee. By the time Bertrand Might was six months old, it was clear something was amiss. His muscles weren’t developing normally; he was…

  • Congratulations to the 2023 Early Career Leadership Program Cohort!

    The Genetics Society of America (GSA) is excited to announce the latest cohort of student, postdoc, and early-career research leaders joining the Early Career Leadership Program.  Participants receive training and mentoring while serving on committees charged with understanding the needs, interests, concerns, and challenges of early career scientist members of the GSA. As part of…

  • 64th Annual Drosophila Research Conference March 1–5, 2023 Chicago, IL and online

    GSA LOCI: Local Outreach Community Initiatives @ GSA Conferences

    Highlights: Local Outreach Community Initiatives (LOCI): The Genetics Society of America is committed to supporting the communities of the host cities of our conferences. This new year, we are excited to reconnect with our GSA community in meaningful ways within and beyond our existing programming. The GSA membership has created a caring and supportive environment…

  • Headshots of the 5 elected members of the GSA Board of Directors on a black background.

    New members of the GSA Board of Directors: 2023–2025

    We are pleased to announce the election of five new leaders to the GSA Board of Directors: 2023 Vice President/2024 President Mariana Wolfner Distinguished Professor of Molecular Biology and Genetics and Stephen H. Weiss Presidential Fellow My research has focused on the genes and pathways that mediate sexual development and reproduction, primarily in Drosophila. From…

  • Lance David Miller

    Lance David Miller: Lighting Your Own Fire by Finding the Right Resources

    By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…

  • Graça Almeida-Porada: The Importance of Communication in a Technologically Advancing World

    By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…