Afferent feedback plays a critical role in the control of locomotion and in the recovery afforded by body-weight supported treadmill training or graft 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 the modality and/or origin of the afferent feedback in recovery have been for the most part unexplored. We propose to integrate a neural model of the locomotor circuitry developed at Drexel University College of Medicine with a biomechanical hindlimb model developed at Georgia Institute of Technology, and to use this integrated model to study the roles of afferent feedback in the control of locomotion under normal conditions and in the absence of sensory feedback. We will demonstrate using the integrated model that in the intact cat the control of locomotion is dependent on afferent feedback from the hip muscles for the initiation of swing while afferent feedback from the ankle extensors and/or cutaneous input from the foot pad are critical to the control of stance. We hypothesize that in the cat with spinal cord injury, training or neurotrophin producing transplants enhance the synaptic strengths of the sensory feedback and that these increases allow the circuitry to produce a stable locomotor pattern in the absence of supraspinal control. The model developed will allow us to investigate this hypothesis and make predictions about the motor pattern deficits obtained when certain sensory modalities are removed after spinal cord injury. Experiments with partially deafferented or re-innervated muscles will allow us to test these predictions and further refine the model. The proposed multidisciplinary project is a collaboration between investigators at Drexel University College of Medicine and Georgia Institute of Technology. Experiments are planned at both locations to identify model parameters and verify the model's predictions. The experimental and modeling work will provide new and important information about the roles of sensory feedback in locomotor recovery after SCI. The intellectual merit of this proposal has several components. First, a comprehensive neuromechanical model of spinal locomotion will be developed that includes the cat hindlimb, motion-dependent proprioceptive feedback, and central pattern generator (CPG). Second, model parameters including feedback weights, modality, and connectivity patterns within CPG will be identified by matching simulated normal and spinal locomotion characteristics with those recorded experimentally. Third, several hypotheses about the role of sensory feedback in locomotion post-SCI will be tested using model simulations and experiments. The results of the model will increase our understanding of the spinal locomotor circuitry and may guide rehabilitation training efforts in individuals with spinal cord injury. The proposal will have broader impacts on the interdepartmental Neuroengineering program at Drexel University, the Neuroscience program at The College of Medicine, and the Applied Physiology and Biomedical Engineering programs at Georgia Institute of Technology by supporting students and a postdoctoral fellow from the programs and providing them with the opportunity to truly integrate computational and experimental neurophysiological concepts acquired in the educational programs. We also expect the models developed in the project to be used in classes taught by Drs. Lemay and Prilutsky on the neural control and biomechanics of locomotion at their respective institutions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012855-02
Application #
8145652
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
2011-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$328,089
Indirect Cost
Name
Drexel University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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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
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
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