Afferent feedback plays a critical role in the control of locomotion and in the recovery afforded by bodyweight supported treadmill training or grafts of neurotrophin producing cellular transplants after spinal cord injury (SCI). Yet our knowledge of the structure of the locomotor circuitry is limited and the roles of afferent feedback in locomotor recovery have been for the most part unexplored. This multidisciplinary project will integrate a neural model of the locomotor circuitry developed at Drexel University with a biomechanical hindlimb model developed at Georgia Institute of Technology. This integrated model will be used as a test bed to study the role of afferent feedback in the control of locomotion in the intact cat and in the recovery of locomotor function after spinal transection. We hypothesize (and have demonstrated using a simplified model) that muscle length dependent feedback from the hip muscles is critical for the initiation of swing and that force feedback from the ankle extensors and cutaneous input from the footpad are critical for the control of stance. We also hypothesize that in spinal cats, training or neurotrophin producing transplants enhance the synaptic strengths of the sensory feedback and that these increases enable the circuitry to produce a stable locomotor pattern in the absence of supraspinal control. The model will allow us to investigate the above key hypotheses and make predictions about the motor pattern deficits obtained when certain sensory modalities are removed after SCI. Experiments with partially deafferented or re-innervated muscles (muscles without length feedback) will be performed to test these predictions and further refine the model.
The aims of this project are consistent with the mission of the National Institute of Biomedical Imaging and Bioengineering to develop and accelerate the application of biomedical technologies and integrate the physical and engineering sciences with the life sciences to advance basic research and medical care. The insights obtained through the model and experimental studies about the roles of afferent feedback in locomotor recovery following SCI may guide rehabilitation training efforts in individuals with spinal cord injury.

Public Health Relevance

Sensorimotor re-training is widely used in rehabilitation to improve the conditions of individuals who have suffered a neurological injury. The model developed in this project will further our understanding of how sensory feedback affects locomotor training following spinal cord injury and may become a useful tool for developing and enhancing locomotor rehabilitation programs for spinal cord injured individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012855-04
Application #
8537456
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (51))
Program Officer
Peng, Grace
Project Start
2010-09-20
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$303,411
Indirect Cost
$71,097
Name
Drexel University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Klishko, Alexander N; Farrell, Bradley J; Beloozerova, Irina N et al. (2014) Stabilization of cat paw trajectory during locomotion. J Neurophysiol 112:1376-91
Markin, Sergey N; Lemay, Michel A; Prilutsky, Boris I et al. (2012) Motoneuronal and muscle synergies involved in cat hindlimb control during fictive and real locomotion: a comparison study. J Neurophysiol 107:2057-71
Pantall, Annette; Gregor, Robert J; Prilutsky, Boris I (2012) Stance and swing phase detection during level and slope walking in the cat: effects of slope, injury, subject and kinematic detection method. J Biomech 45:1529-33
Spardy, Lucy E; Markin, Sergey N; Shevtsova, Natalia A et al. (2011) A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: I. Rhythm generation. J Neural Eng 8:065003