What does a worm’s nervous system tell us about disorders like Huntington’s Disease?
A fascinating new discovery by scientists from Mount Sinai’s Samuel
Lunenfeld Research Institute published in the leading journal Neuron is
laying the groundwork for alternative and effective future therapies
that will help restore coordination in movements for patients suffering
from neurodegenerative disorders such as Huntington’s disease,
Parkinson’s, ALS and others.
And the source of the discovery? A worm’s nervous system.
Years of work by Dr. Mei Zhen, Lunenfeld Senior Investigator, and her research team have led to the discovery of how motor behaviours use inputs from the brain and the environment to achieve efficient coordination. By studying the motor circuitry of C. elegans, a worm, Dr. Zhen’s team was able to isolate not only specific groups of neurons, but also the specific connections and properties of these neurons that control specific movements.
“With this discovery, we’re building the knowledge foundation of future treatment for neurological disorders,” says Dr. Zhen. “My expectation is that these new studies and insights will be applied to help patients with disorders that affect their balance and coordination.”
She adds, “There are so many basics that we do not yet know – like how neurons manage to work together as a network. They must be precise. We would not be able to take a single step if they mess up with one command to our muscles. At the same time, they have so much flexibility. If we can figure these principles out, we can develop methods to improve muscle control in patients that lose that ability.”
In this study, Dr. Zhen’s research team teamed up with researchers at Harvard and MIT to analyze the different groups of neurons in the C. elegans worm in order to learn how they activate sequentially, and to achieve a complex outcome such as directional movement. In other words, how does a worm move like a worm?
This study shows that one class of neurons can instruct neighbouring neurons to activate or inactivate. This allows them to work as a group, in a precise sequential order, to result in smooth movement.
The C. elegans roundworm has been used as a model for the nervous system since the 1960s, and Dr. Zhen’s team has been studying the motor circuit of the C. elegans worm for over ten years. Compared to billions of neurons in the human brain, C. elegans has a basic nervous system with only a few hundred neurons that make a few thousand connections.
Dr. Zhen’s research group is a leader for probing the C. elegans nerve circuitry in real time with genetic calcium fluorescent markers. This enables them to monitor how the patterns of activity are generated between neurons, and how these contribute to the assembly of coordinated behaviours.
Indeed, as Dr. Zhen notes, most people do not realize the intricacy our mind generates to coordinate each muscle contraction in order to take a single step.