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.

Public Health Relevance

Project Narrative We propose to provide, for the first time, a clear and consistent view of signaling from primary motor cortex to spinal motoneurons. Results from the proposed experiments will address fundamental issues about the organization and function of motor cortex, its role in the generation and control of movements and the nature of motor cortex output. These results can provide insight into loss of motor functions following damage to M1 and lead to new rehabilitation approaches. Further, these results will be important for providing information necessary in the design of neuroprosthetic devices which use signals from the motor cortex to control robotic devices or control electrical stimulation of muscle activity to restore motor function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS070366-01A1
Application #
8122630
Study Section
Special Emphasis Panel (ZRG1-F02B-M (20))
Program Officer
Chen, Daofen
Project Start
2011-07-01
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$51,326
Indirect Cost
Name
University of Pittsburgh
Department
Biology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Griffin, Darcy M; Hoffman, Donna S; Strick, Peter L (2015) Corticomotoneuronal cells are ""functionally tuned"". Science 350:667-70