(Toronto, ON) In the first study of its kind worldwide, scientists at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, in collaboration with researchers at the University of Toronto and the Chinese University of Hong Kong, have uncovered a new concept to explain how directionality of movement is achieved in the model organism, C. elegans. The findings represent a significant step forward in understanding the motor systems of invertebrates and vertebrates alike, and will shed new mechanistic insights into how motor circuits generate coordinated behaviours and how their dysfunction may lead to motor disorder illnesses.
The study was published online today in the leading neuroscience journal, Neuron.
Previous studies had revealed the core components of the nematodemotor circuit, which has proven to be an ideal model for understanding how complex neuronal networks operate. But until now, it was unclear just how the worm coordinated and executed bi-directional movement, specifically how its motor circuit selects and alters the direction of movement. The new discovery changes the way that scientists think about how muscle controls coordinate movement.
“We have shown that imbalanced forward and backward motoneuron activity determines directionality, and that C. elegans alternates between these states to change directions,” said Dr. Mei Zhen, lead author of the study and a Principal Investigator at the Lunenfeld.
Using extremely precise fluorescent calcium imaging capable of tracking the activity of multiple neurons in a moving and behaving animal, as well as electrophysiology and behavioural analyses of normal and mutant animals, Dr. Zhen’s team correlated motor circuit activity with motion, revealing some of the fundamental mechanisms underlying motor circuit operations.
The researchers found that, contrary to previously accepted theories, the “on” or “off” activity of a specific class of motoneurons (governing movements of different directionalities) establishes an anti-correlated pattern: increased activity of one class of motoneuron correlates with the decreased of activity of the other class, and viceversa. Such a reversed pattern leads to an immediate switch in directionality.
Moreover, Dr. Zhen and colleagues revealed that junctions between interneurons and motor neurons play an unexpected role in this process. Specifically, in the backward circuit, a specific type of junction between interneurons—the interface between sensory and motoneurons—and motor neurons reduces the ability of interneurons to activate motor neurons. This maintains the backward circuit in a low activity state—creating an inherent bias of the motor circuit to generate an output pattern that favours forward movements.
The result: a real-time observation of coordinated motor circuit activity and a new model that can be applied to other animal systems aimed at understanding how motor behaviours are generated. The findings provide insight into the development of new therapeutic targets for uncoordinated motor behaviours in illnesses including Huntington’s and Parkinson’s disease.
“Our findings are particularly exciting because this study sets a new precedent for assessing the nervous system in behaving animal models,” said Dr. Zhen. “This is one of the first studies in which we have traced the steps that are integral to how neural circuits establish specific behaviours.”
The study was funded by the EJLB Foundation and was made possible through the post-graduate and PhD work by Taizo Kawano, Michelle Po, and Shangbang Gao.