Grant: Project Grant

Muscles generate a wide range of forces, from delicate levels needed to insert a contact lens to high force movements in regaining lost balance. This range is determined by activity in the brain and spinal cord, and ultimately by output from spinal motoneurons that connect to muscles and determine strength of muscle contractions during a movement. The ability of motoneurons to respond to signals from the brain and other sources are important for generating increased force when required. Key to this process is the control of motoneuron excitability, which is tunable to physical demands for movement. Our work is focused on spinal neurons, called V0c neurons, that control (i.e., tune) motoneuron excitability, and therefore serve as critical gatekeepers of motoneuron output strength. We have found special connections called electrical synapses between V0c neurons that allow them to be synchronously or collectively active. We propose that these connections greatly enhance V0c neuron control of motoneuron output. Using experimental mouse models, we will determine how V0c neurons contribute to force level control in the limbs. We will: i) map the connections of these neurons to different classes of motoneurons; ii) measure the extent to which electrical synapses between these V0c neurons promote their synchronous activity; and iii) assess how brain and spinal cord circuitry engage V0c neurons to facilitate collective motoneuron activity. This work will determine the role V0c neurons play in the control of muscle force generation. We expect our results will challenge current textbook knowledge on force generation during movement, and reveal new concepts on how command signals to motoneurons are converted to desired levels of muscle activity. This research will enable designs of regeneration and rehabilitation therapies to regain strength and muscle activity in spinal cord injury and disease.