Following spinal cord injury, alterations occur in the properties of spinal motoneurons and in the excitatory and inhibitory synaptic pathways that converge upon them. This plasticity has been considered an adaptive response to injury, compensating for loss of descending drive. Alternatively, such alterations may be maladaptive, contributing to muscle spasticity and coactivation of antagonist muscle groups following injury. The plasticity of the spinal cord also offers the promise of therapies to restore function and ameliorate adverse effects following spinal cord injury through such measures as locomotor training and reflex conditioning. In this project we will identify changes in the organization of motoneuron pools following incomplete spinal cord injuries, the effect of locomotor training on these changes, and the impact of these changes on motoneuron pool function. These studies will be conducted using a rat model of incomplete spinal cord injury in which a spinal cord injury is produced by contusion while the animal is deeply anesthetized. Uninjured rats will be compared to those with incomplete spinal cord injury and to rats with incomplete spinal cord injury given access to voluntary locomotor exercise. These groups of rats will be compared with respect to 1) the strength and distribution in a motoneuron pool of a reflex source and a central (descending and propriospinal) source of synaptic excitation;2) the strength and distribution of a reflex source of synaptic inhibition;and 3) the contractile properties of muscle fibers innervated by this group of motoneurons. The organization of each of these systems will be characterized according to the intrinsic properties of the motoneurons and their discharge characteristics. The functional impact of changes produced by incomplete spinal cord injury and by exercise therapy following injury will be assessed by simulation, using a dynamic model of an antagonist pair of motoneuron pool-muscles whose parameters incorporate the changes in synaptic, motoneuron pool and muscle organization observed in these studies. The overall goal of this project is to gain an understanding of the effects of a common type of spinal cord injury on the organization and function of a motoneuron pool and the muscle it controls and to assess the benefits and limitations locomotor training.

Public Health Relevance

The overall goal of this project is to gain an understanding of the effects of a common type of spinal cord injury on the organization and function of a motoneuron pool and the muscle it controls and to assess the benefits and limitations of locomotor training. The motoneuron pool - muscle complex is the basic unit of movement control at the level of the spinal cord movement generation and control. This research will increase our understanding of the plasticity of this fundamental unit of movement control, how it changes following spinal cord injury, and its response to exercise therapy, information that is important for development of new therapies to assist patients with incomplete spinal cord injuries.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01NS082463-02
Application #
8729035
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Jakeman, Lyn B
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
St. Joseph's Hospital and Medical Center
Department
Type
DUNS #
City
Phoenix
State
AZ
Country
United States
Zip Code
85013