Master neuron that controls movement in worms discovered, important for treating humans

Researchers from Sinai Health and the University of Toronto have discovered a mechanism in the nervous system of the small roundworm C. Elegans that could have significant implications for the treatment of human diseases and the development of robotics.

The study, led by Mei Zhen and her colleagues at the Lunenfeld-Tanenbaum Research Institute, was published in Science Advances and reveals the key role of a specific neuron called AVA in controlling the worm's ability to switch between moving forward and backward.

It is extremely important for worms to crawl towards food sources and quickly retreat from danger. This behavior, when two actions are mutually exclusive, is typical of many animals, including humans, who cannot sit and run at the same time.

Scientists have long believed that movement control in worms is accomplished through simple mutual actions of two neurons: AVA and AVB. The former was thought to promote backward movement and the latter to forward movement, each suppressing the other to control the direction of movement.

However, new data from Zhen's team challenges this notion, revealing a more complex interaction where the AVA neuron plays a dual role. Not only does it immediately stop forward motion by suppressing the AVB, but it also maintains long-term AVB stimulation to ensure a smooth transition back to forward motion.

This finding highlights the ability of the AVA neuron to finely control movement through different mechanisms depending on different signals and on different time scales.

"From an engineering point of view, this is a very cost-effective design," says Zhen, a professor of molecular genetics in the Temerty Faculty of Medicine at the University of Toronto. "Strong and sustained suppression of the feedback circuit allows animals to respond to unfavorable conditions and escape. At the same time, the control neuron continues to supply constant gas to the forward circuit to move to safe places."

Jun Meng, a former doctoral student in Zhen's lab who led the study, said that understanding how animals transition between such opposing motor states is key to understanding how animals move, as well as to research into neurological disorders. p>

The discovery of the dominant role of the AVA neuron offers new insight into neural circuitry that scientists have been studying since the advent of modern genetics more than half a century ago. Zhen's lab has successfully used advanced technology to precisely modulate the activity of individual neurons and record data from live worms in motion.

Zhen, also a professor of cell and systems biology in the Faculty of Arts and Sciences at the University of Toronto, emphasizes the importance of interdisciplinary collaboration in this research. Meng conducted the key experiments, and the electrical recordings of the neurons were performed by Bing Yu, Ph.D., a student in Shanban Gao's lab at Huazhong University of Science and Technology in China.

Tosif Ahmed, a former postdoctoral fellow in Zhen's lab and now a theoretical fellow at the HHMI Janelia Research Campus in the United States, led the mathematical modeling that was important for testing hypotheses and generating new knowledge.

AVA and AVB have different membrane potential ranges and dynamics. Source: Science Advances (2024). DOI: 10.1126/sciadv.adk0002

The study results provide a simplified model for studying how neurons can orchestrate multiple roles in movement control, a concept that can be applied to human neurological conditions.

For example, AVA's dual role depends on its electrical potential, which is regulated by ion channels on its surface. Zhen is already investigating how similar mechanisms may be involved in a rare condition known as CLIFAHDD syndrome, caused by mutations in similar ion channels. The new findings could also inform the development of more adaptive and efficient robotic systems capable of performing complex movements.

"From the origins of modern science to cutting-edge research today, model organisms such as C. Elegans play an important role in unlocking the complexity of our biological systems," said Anne-Claude Gingras, Lunenfeld-Tanenbaum Research Institute director and vice president by research at Sinai Health. "This research is a great example of how we can learn from simple animals and apply that knowledge to advance medicine and technology."