Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research on repetitive worm behavior may have implications for understanding human disease

13.05.2019

Repetition can be useful if you're trying to memorize a poem, master a guitar riff, or just cultivate good habits. When this kind of behavior becomes compulsive, however, it can get in the way of normal life--an impediment sometimes observed in psychiatric illnesses like Tourette's syndrome and autism spectrum disorders. Now, Rockefeller scientists have identified a brain circuit that underlies repetition in worms, a finding that may ultimately shed light on similar behavior in humans.

Studying the microscopic roundworm C. elegans, the researchers found that defects in one protein cause animals to reorient themselves over and over again. Described in Nature Communications, these observations are bolstered by previous research in mice, and suggest that similar mechanisms may drive repetitive behavior in a range of animals, including humans.


Human astrocytes are important for brain signaling. Researchers are gaining new insights into their function by studying their worm equivalent.

Credit: Laboratory of Developmental Genetics at The Rockefeller University

Usage Restrictions: Image may be used to illustrate the research described in the accompanying release.

Chemical cleanup

The scientists initially set out to understand how astrocytes, star-shaped cells found in mammalian brains, help neurons do their job. Astrocytes are thought to be responsible for, among other things, disposing of excess neurochemicals at synapses, the connections between neurons.

This task is vital because if chemicals are not removed in a timely fashion, they can stimulate neurons in unexpected ways, disrupting normal brain function. To better understand this process, Menachem Katz, a research associate in the lab of Shai Shaham, looked to C. elegans CEPsh glial cells, which he suspected to be the worm equivalents of astrocytes.

Confirming this suspicion, Katz, Shaham, and their colleagues, used mRNA sequencing to show that mouse astrocytes and CEPsh glia have similar genetic signatures. Among other commonalities, both cell types produce the protein GLT-1, the mammalian version of which is responsible for clearing the chemical glutamate away from synapses. This finding, says Shaham, afforded the researchers a unique opportunity to define how astrocytes and GLT-1 work.

"Scientists have been trying to understand the functions of astrocytes for many years, and in mammals it's not easy because these cells are essential for keeping neurons alive," he says. "But in C. elegans there are only four CEPsh glial cells, and they are not required for neuron survival. This allowed us to investigate the specific roles of glutamate transporters, without worrying about the side effects of neuron sickness."

To do so, the researchers created C. elegans lacking GLT-1. Surprisingly, this depletion did not result in glutamate accumulation at synapses, as was expected. Instead, the worms exhibited oscillations in synaptic glutamate levels--and a peculiar behavioral defect.

"These animals changed their direction at a crazy rate. They just kept moving forward and going back, moving forward and going back," says Shaham, the Richard E. Salomon Family Professor. "And when we analyzed this behavior, we discovered that they did so in a really interesting pattern."

Turn, turn, turn

It's perfectly normal for C. elegans to change course every now and then. Typically, the worm reorients itself about once every 90 seconds. But worms lacking GLT-1, the researchers found, took this action to the extreme: at 90 second intervals the animals executed not one reversal, but bursts of them. "It's as if once they start the action, they can't stop repeating it," says Katz.

Further experiments revealed that removal of the glutamate receptor MGL-2 blocked both repetitive reversals and synaptic glutamate oscillations. The researchers concluded that when glutamate is not efficiently cleared, the chemical stimulates MGL-2, which in turn triggers the release of yet more glutamate. This process then repeats on a loop; and every time glutamate is released, it activates the neuron responsible for initiating reversals.

"These findings suggest a simple model for how repetition can occur in worms," says Katz. "And, it turns out, this model may hold up in more complex nervous systems."

Indeed, past experiments have shown that GLT-1 mutations cause repetitive grooming in mice, and that compounds blocking the mouse version of MGL-2 eliminate similar behavior in other contexts. Taken together with the new findings in C. elegans, this research suggests that abnormal glutamate secretion may underlie repetitive behaviors across the animal kingdom--raising the possibility that they may be relevant to understanding pathological repetition in humans.

Consistent with this idea, human genetics studies have found mutations associated with glutamate signaling in patients with obsessive compulsive disorder and autism spectrum disorders, both of which can be accompanied by repetitive behavior.

"We were really excited to see these links in the scientific literature because it means our findings may help uncover a plausible mechanism underlying an important class of human diseases," says Shaham. "And, more broadly, we're showing that candidate genes affected in human disease can be studied and verified in the simpler worm."

Media Contact

Katherine Fenz
kfenz@rockefeller.edu
212-327-7913

 @rockefelleruniv

http://www.rockefeller.edu 

Katherine Fenz | EurekAlert!
Further information:
https://www.rockefeller.edu/news/25817-research-repetitive-worm-behavior-may-implications-understanding-human-disease/
http://dx.doi.org/10.1038/s41467-019-09581-4

Further reports about: Astrocytes elegans glial cells glutamate neurons oscillations synapses

More articles from Life Sciences:

nachricht "Make two out of one" - Division of Artificial Cells
19.02.2020 | Max-Planck-Institut für Kolloid- und Grenzflächenforschung

nachricht Sweet beaks: What Galapagos finches and marine bacteria have in common
19.02.2020 | Max-Planck-Institut für Marine Mikrobiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

"Make two out of one" - Division of Artificial Cells

19.02.2020 | Life Sciences

High-Performance Computing Center of the University of Stuttgart Receives new Supercomuter "Hawk"

19.02.2020 | Information Technology

A step towards controlling spin-dependent petahertz electronics by material defects

19.02.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>