The proposed experiments will elucidate the integration of descending and sensory signals by interneuronal pathways in the cervical spinal cord of the behaving monkey. The long-term objective of the work is to understand the contribution of spinal cord circuits to the control of normal and impaired voluntary movements of the primate arm. Ultimately, the work will lead to a search for therapies and interventions that can overcome the motor deficits associated with spinal cord injury and stroke.
The specific aims of the project examine two broad issues. First, what are the mechanisms by which spinal interneuronal pathways integrate descending and feedback information to regulate the amplitude and timing of wrist and hand muscle activity during voluntary movements? Second, how does information processing in spinal pathways adapt muscle activity to expected and unexpected mechanical conditions? The activity of interneurons in the C5-T1 spinal segments will be recorded in awake monkeys performing several voluntary motor tasks with different instructions and under different loading conditions. These behaviors will include ballistic and slow tracking movements of the wrist, power and precision grips of the hand, and a reach-and-grasp task. The connectivity of the neurons will be identified with spike-triggered averages of muscle activity, and natural and electrical stimulation of peripheral afferents and descending pathways. Mechanical perturbations will be applied to test for the contribution of specific feedback pathways to ongoing and compensatory muscle activity. Neurons in primary motor cortex will be studied under the same conditions. Comparison of cortical and spinal responses will explore the nature of corticospinal processing during execution of voluntary arm and hand movements.

Public Health Relevance

The experiments will provide new insights into the contribution of the primate spinal cord to the generation of a varied repertoire of accurate and flexible movements of the arm and hand. This information is essential for understanding spinal mechanisms of motor impairment and recovery following central nervous system injury. The project will lay the foundation for future studies on possible therapies or interventions to improve recovery from stroke and spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS049447-01A2
Application #
8004466
Study Section
Special Emphasis Panel (ZRG1-IFCN-L (03))
Program Officer
Chen, Daofen
Project Start
2010-09-01
Project End
2012-06-30
Budget Start
2010-09-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$669,845
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Powers, Berit E; Lasiene, Jurate; Plemel, Jason R et al. (2012) Axonal thinning and extensive remyelination without chronic demyelination in spinal injured rats. J Neurosci 32:5120-5