What language does the motor cortex use to speak to motoneurons? The primary motor cortex (M1) is a major source of descending commands to the spinal cord for generating motor output. Approximately 50% of the corticospinal neurons from the frontal lobe originate from M1. A special set of these corticospinal neurons are corticomotoneural (CM cells) which have direct connections to motoneurons. We will investigate CM cells using a combination of behavioral, electrophysiological and anatomical methods. We propose to provide, for the first time, a clear and consistent view of signaling from CM cells to motoneurons. We will identify CM cells and their target muscles using spike-triggered averaging (SpTA) of electromyographic (EMG) activity. The activity of CM cells and their target muscles will be investigated in relation to wrist movements involved in a multi-directional wrist task capable of dissociating intrinsic (muscle-like) and extrinsic (movement-like) parameters of wrist movement. Previous studies have shown that both intrinsic and extrinsic parameters are present in M1 activity (Kakei et al., 1999). One way to explain the presence of both muscles and movements is the existence of a hierarchy. The hierarchy hypothesis would predict that CM cell activity is muscle like and non-CM cell activity is movement like. In other words, direct input to motoneurons is in a language that does not need to be translated. The alternative is that a mixture of muscle-like and movement-like activity reaches the motoneuron and is used to create movements under different conditions. This project will determine which hypothesis is correct. We will also document, for the first time, the location and distribution of CM cells projecting to wrist muscle motoneurons. We will use the transneuronal transport of rabies virus to define the location of CM cells in the motor cortex that influence antagonist wrist muscles; flexor carpi radialis and extensor carpi radialis. If time permits, we will compare the distribution of CM cells in naive animals to those of animals trained to perform a skilled wrist task. This experiment will enable us to determine whether extensive training alters the cortical territory of CM cells in M1.