Control of movement: regulation of spinal-muscular circuits

Quality and longevity of life may be significantly impacted by diseases or injuries affecting the spinal cord. One disability resulting from such diseases and injuries is the reduction in or loss of the ability to move. This application addresses neural circuits between the spinal cord and muscles that ensure that limbs move appropriately during behaviour. The nerve cells that cause muscles to contract are called "alpha motor neurons." These nerve cells receive commands from many other types of nerve cells in the spinal cord, process these commands, and send messages to muscles causing them to contract. The muscles in turn can relay information about their position and their speed of contraction back to the spinal cord. Much of this sensory information is carried by sensory nerve fibres receiving information from organs embedded within the muscle called "muscle spindles." These spindles are controlled other nerve cells in the spinal cord called "gamma motor neurons." Little is known about the control of these gamma nerve cells. In this application, I propose to study alpha and gamma motor neurons, and the ways by which the activity of these nerve cells is controlled to ensure that limbs move appropriately during behaviour (walking). These studies involve a number of cutting edge techniques in which we will use transgenic mice and advanced microscopy techniques which together allow visualisation and manipulation of the activity of identified nerve cells. In addition, we propose to genetically modify these neurons to study the mechanisms underlying the control of these neurons in behaviour. By the conclusion of the 5-year granting period, we will have a greater understanding of the communication between the spinal cord and muscles. Knowledge of this circuit will assist in the development of strategies to improve the function of people living with spinal cord injuries and diseases.