The basic motor patterns driving the rhythmic movements of our lower limbs during walking are generated by groups of neurons termed central pattern generators (CPGs) which are located within the spinal cord. The Iocomotor CPG is strongly influenced by timing information from ongoing afferent feedback, particularly those provided by hip flexion and limb loading, but also by more specialized 'resetting'responses (e.g. stumble-corrective). After a complete thoracic spinal cord injury (SCI), control of the hindlimb CPG is wholly dependent on remaining sensory afferent activity patterns, and under the right conditions, the sensorimotor transformations are so well encoded that treadmill locomotion in the adult rat is almost indistinguishable from a normal animal (Courtine et al. 2009). Limb afferent feedback alone was able not only to encode treadmill speed changes, but also produced movement synergies needed for sideways and backward stepping. The spinalized thoracolumbar neonatal rat spinal cord can be maintained in vitro with the hindlimbs attached. While the neonate is incapable of weight bearing locomotion, the isolated in vitro preparation is capable of generating complex hindlimb locomotor patterns with motor synergies that are surprisingly similar to those observed electromyographically and kinematically in the adult. If the afferent encoding properties are also similar at this age, there is an opportunity to study afferent control of locomotor spinal networks with the mechanistic strength on an in vitro preparation. We have developed a neonatal mouse locomotor preparation that features an optimized peripheral nerve dissection for selective stimulation of cutaneous and muscle afferents and are thus in an unprecedented position to characterize afferent actions on the CPG. Advances in our understanding of sensory input on movement control will allow us to define more precisely the requirements for the rehabilitation of patients with SCI. There is increasing evidence that in order to treat patients that have suffered an SCI more effectively, therapeutic strategies should include a combination sensory afferent stimulation techniques (e.g. epidural stimulation) and assisted physical therapy. Our findings will have direct implications for better designing these therapeutic strategies designed to take advantage of the plasticity of the spinal CPG network for locomotion.

Public Health Relevance

A detailed understanding of the pathways enabling sensory-motor transformations during locomotion promises to provide a roadmap for designing effective interventions to promote locomotor function following SCI. The advantage of this animal model system is the ability to use approaches and technologies that promise to greatly accelerate our discovery of these essential pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103642-02
Application #
8687684
Study Section
Special Emphasis Panel (ZGM1-TWD-B)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$247,041
Indirect Cost
$82,347
Name
University of Puerto Rico Med Sciences
Department
Type
DUNS #
948108063
City
San Juan
State
PR
Country
United States
Zip Code
00936
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