Exploring a Role for Sleep in Regulating Skeletal Muscle Physiology

Skeletal muscles are remarkably adaptive tissues, with the ability to both modify their phenotypic properties in response to altered functional demands and to recover from serious injury. One mechanism through which changes in physiological and environmental conditions are signaled to muscles is via neural input from motoneurons. During sleep, neural input to the musculature is generally reduced; however, the association between the contractile phenotype of a muscle and its motor activity in sleep is unclear. Moreover, it is unknown whether sleep motor control has a functional influence on muscle physiology. I used an array of electrophysiological, molecular, histological and functional techniques in both naturally-behaving and anaesthetized rats to test the hypothesis that sleep influences skeletal muscle physiology, both under normal conditions and in response to muscle injury. The key findings of my thesis project are the following: 1. The contractile phenotype of a muscle can, in part, predict the degree of muscle tone suppression in non-rapid eye movement (NREM) sleep and phasic activity in REM sleep. Muscle activity of a fast-twitch muscle is potently suppressed in NREM sleep and its phasic activity is enhanced in REM sleep compared to waking, whereas a slow-twitch muscle experiences a low degree of suppression in NREM sleep and less phasic activity in REM sleep compared to waking. 2. Acute sleep restriction does not reverse the sleep-related suppression of fast-twitch muscle activity, ostensibly since enforced waking is characterized by motor behaviour that is distinct from that of spontaneous waking. Moreover, sleep loss does not affect the immediate expression of metabolic and phenotypic molecular markers in either muscle phenotype. 3. Both acute and chronic sleep loss cause impairments in functional muscle recovery following myotoxic injury; specifically, sleep loss is associated with reduced early and medium-term expression of molecular repair markers and contractile function deficits during recovery in a fast-twitch, but not slow-twitch, muscle, although the incidence of newly regenerating muscle fibres in damaged tissue is unaffected by sleep loss. Together, these results suggest that motor regulation in sleep may play a functional role in influencing skeletal muscle physiology, especially during recovery from a severe homeostatic challenge like muscle injury.Ph.D