Grant: Discovery Grants Program - Individual

Movement is a fundamental feature of being a human - we move to eat, breath, reproduce, and meet our needs for maintaining life. All movements are achieved through the activation of motoneurons and their innervated muscle fibres, collectively known as motor units. Force gradations, and the ability to produce a variety of motor behaviours to meet our daily needs, rely on the recruitment of motor units and discharge rate modulation of active motor units. Although motoneurons were once believed to be passive integrators of synaptic inputs (i.e., the net excitation/inhibition they receive), a recent body of literature has revealed that active properties of motoneurons drastically affect their output. Dendritic voltage-sensitive persistent inward currents (PICs) amplify and prolong synaptic inputs and these PICs are facilitated by monoamines (serotonin [5HT]; and norepinephrine [NE]) released from brainstem nuclei via long descending axons to spinal motoneurons. In general, the role of 5HT and NE throughout the central nervous system has received considerable attention because of their potent effects on setting our mood and attention. On the contrary, the role of monoamines in setting the body up for movement has received considerably less attention. Studies concerning the actions of the monoaminergic input to motoneurons in non-human animal models have revealed many potentially intriguing mechanisms for the neural control of movement and dysfunction after neurological impairment, but the methods required to study these inputs in the human have not been available until now. Recent technological developments in surface electromyography (sEMG) electrode design and advanced computing algorithms now allow us to record from tens of motor units simultaneously during variety of human behaviours. As such, we are at the forefront of understanding how pools of motor units control force output and adapt to use and disuse in humans. The purpose of this research program is to study how monoaminergic inputs, specifically those of the serotonergic type, are involved in the neural control of human movement. We will systematically characterize 1) changes in human motoneuron properties during different motor A) intensities (level of effort), B) tasks (isometric, shortening, lengthening contractions), and C) states (i.e., rest vs locomotor behaviour), and 2) the effects drugs that perturb 5HT signalling on intensity-, state- and task-dependent changes in neural excitability. High-density sEMG and blind source separation will allow us to measure the discharge patterns of motor units during voluntary behaviours. Using these non-invasive techniques, we will estimate the biophysical properties of motoneurons across the entire motor pool during a variety of motor tasks, which will help us provide mechanistic insights about the neural control of movement and how motoneuron properties differ when humans perform the plethora of tasks we are capable of.