PROJECT SUMMARY/ABSTRACT Motor units, consisting of a single motor neuron and the set of muscle fibers they innervate, are the final common output of the motor commands. The connection between the motor neuron and its muscle fibers is extremely reliable, making motor neurons the only cells in the central nervous system (CNS) whose output can be readily measured and linked to their functional output (i.e. force generation). Many motor unit pools must accommodate a rich diversity of motor behaviors, including rhythmic repetitive behaviors, volitional movements, and postural maintenance. Our overall goal is to investigate the mechanisms governing the neuromotor control of behavioral diversity. A multiplicity of motor neuron input-output functions has been observed in non-human animal electrophysiological studies, with motor neurons behavior as oscillators, variable gain amplifiers, or integrators. Our overall concept is that these motor neuron electrical states are adaptations to perform distinct functional behaviors. To understand the relationship between these electrical states and motor behaviors, our goal is to use state of the art high-density surface electromyography (EMG) arrays to record motor unit discharge patterns from several chest wall muscles that are active during breathing, volitional movements, and postural maintenance. These discharge patterns contain information about both the descending drive to motor neurons as well as their intrinsic properties. One important factor is the profound effect neuromodulation can have on the intrinsic excitability of motor neurons. Based on electrophysiological studies, neuromodulatory inputs seem to be much more important for posture and volition than for breathing and other lower-force rhythmic activities, which are instead primarily driven by glutamatergic activation of NMDA receptors. A common feature of high levels of neuromodulation is hysteresis in the onset and offset frequency of motor units. On the other hand, NMDA receptors are self-inactivating and thus are unlikely to generate discharge rate hysteresis. In Aim 1, we will use high-density surface EMG arrays to record and subsequently discriminate motor unit discharge patterns from four chest wall muscles in humans during automatic breathing, volitional breathing, and sustained trunk rotations. We hypothesize that discharge rate hysteresis will be positive during volitional breathing and sustained trunk rotations, and nil or negative during automatic breathing. These experiments will identify motor unit discharge pattern signatures, such as discharge rate hysteresis, during distinct functional behaviors that correspond to motor neuron electrical states. In Aim 2, we will employ pharmacological ma...