From genes to function: a deep dive into motoneuron bistability – MOTOBIS

The complexity of motor control continues to astonish neuroscientists. While the brain is often seen as the primary controller of movements, recent studies indicate that motoneurons from the spinal cord, which directly control muscles, play a more pivotal role than once believed. These motoneurons exhibit a unique firing characteristic known as "bistability." This behavior can be likened to a light switch with two positions: 'on' and 'off'. A brief excitation turns it 'on', and it remains so until a brief inhibition switches it 'off'. The 'on' state, marked by a self-sustained tonic spiking activity, seems ideal for motor tasks like posture. However, the role of bistable motoneurons in motor control remains enigmatic. Based on our previous publications on the subject (Nat. Medicine, Nat. Comm, Cell Reports...) and promising preliminary data, the project aims to elucidate the role of bistability in motor functions both under normal conditions and in the context of spasticity (hypertonia) that arises after a spinal cord injury.
To effectively execute this project, we leverage the established collaboration among three partners, each bringing distinct yet complementary expertise spanning from molecular insights to computational and integrative neurosciences. The project is structured into 3 main axes: 1) A transcriptomic study of bistable motoneurons, focusing on ion channels and motoneuron typology, supplemented by research into their presence in humans. 2) An investigation into the influence of bistability on motor functions, especially postural ones, shedding new light on the established dogma of the size principle regarding motoneuron recruitment. 3) A study of the alterations of bistability associated with spasticity. We are confident that this work will stand as a benchmark in the field, paving the way for innovative therapeutic approaches.