We plan to investigate the neural mechanisms controlling voluntary limb movement in primates. The functional roles of premotor (preM) cells in motor cortex and spinal cord will be directly compared. PreM cells with a correlational linkage to forelimb motoneurons will be identified by post- spike effects in spike-triggered averages of EMG activity. The activity of PreM cells and multiple muscles will be documented during movements of the wrist in different directions. Monkeys will operate a multi-jointed manipulandum that will allow wrist movements in three directions: flexion- extension, radial-ulnar deviation and pronation-supination. In addition a grip handle will transduce force during a power grip. This repertoire of movements will activate muscles in different synergistic combinations [e.g., some muscles are synergists in flexion-extension, but become antagonists in radial-ulnar deviation]. We will determine whether PreM cells are organized primarily in terms of movements or muscles -- i.e., whether they are recruited in relation to all movements that involve their target muscles or only specific ones. We anticipate finding functionally significant differences between motor cortex cells and spinal interneurons with regard to their postspike effects on muscles and their relation to movements. Spinal cord interneurons have been studied largely in immobilized animals, so our study of spinal PreM interneurons will provide unprecedented information about the activity and output effects of interneurons during normal active movements. To identify these interneurons further, we will document their synaptic inputs from different forelimb muscles and from functionally identified cortical sites. Synaptic interactions between motor cortex cells will be investigated with in vivo intracellular recordings; using extracellular spikes recorded simultaneously from neighboring neurons, we will compile spike-triggered averages of membrane potentials. This will document unitary post-synaptic potentials (PSPs) produced between cells in different cortical layers. We will also examine the mechanisms which modulate synaptic efficacy in vivo. These studies will provide information essential to understanding and further investigating clinical motor disorders, like cerebral palsy, stroke and epilepsy.