SPINAL PLASTICITY OF A CORRECTIVE KINEMATIC RESPONSE

University Of California Los Angeles, Los Angeles CA

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Abstract

Motor learning in the mammalian spinal cord following a complete spinal cord transection (ST) suggests a remarkable level of neuronal plasticity in the absence of supraspinal input. For example, ST cats and rats can learn to perform motor tasks such as stepping and standing. Furthermore, the spinal cord can sense, respond to, and successfully learn to overcome a perturbation to the step cycle. The neural mechanisms that underlie these complex decision-making events within the spinal cord are unknown. The central hypothesis of this proposal is that the mammalian lumbar spinal cord has the capability to normalize the kinematics of the hindlimbs in response to a perturbation in the swing phase of a step cycle, and that these adaptive events are mediated by molecular mechanisms similar to those associated with learning in the brain. The ability of the spinal cord to generate a corrective kinematic response will be examined using a robotic system developed in this laboratory, which will impose a programmed perturbation during the step cycle and then to quantify the kinematic response. The proposed experiments will characterize the kinematic and physiological adaptations to swing phase force field induced learning by the lumbar spinal cord in ST rats. Selective neural substrates and specific pathways associated with the adaptive responses will be examined using pharmacological, anatomical and biochemical approaches to gain insight into the physiological and molecular mechanisms to which these learning and memory events can be attributed. Phosphorylated cyclic AMP binding element protein will be measured using Western blots and immunohistochemistry in retrogradely identified flexor and extensor motor pools that execute kinematic control. Biochemical adaptations in the signaling pathways in the lumbar spinal cord will be correlated with dose dependent inhibition of the response using protein synthesis inhibitors. These studies will allow us to begin to identify physiological and cellular events that may underlie spinal motor learning, and provide a framework around which strategies for use-dependent therapeutic procedures following neural injury in human patients can be developed. It is apparent that in order to facilitate recovery of motor function after spinal cord injury or stroke, it is important to train the motor task behavior in a kinematically correct pattern. Understanding the physiological and cellular mechanisms by which motor learning occurs will provide a better understanding of how spinal neural pathways that control posture and locomotion are influenced by use-dependent mechanisms.