It is becoming increasingly clear that providing functional restoration presents novel computational problems to the CNS. There are several serious gaps in our understanding of processes that support the functional recovery that occurs after neonatal spinal transection lesions and the processes that, by their absence, cause failure of recovery in adult lesions. Understanding the motor processes that mediate weight support in spinal injured rats will improve therapies (such as regeneration, training, or neural prostheses) aimed at enhancing locomotor recovery. We have shown that changes in cortical representations and control of paraspinal muscles may play a key role in weight support following neonatal injury in spinal rats. Paraspinal muscles coordinate the pectoral and pelvic limb mechanics. The mechanical actions of paraspinal muscles may also assist in indirect coupling processes that coordinate pattern generators and motor primitives among the limbs through propriospinal and proprioceptive loops. The goal of this proposal is an investigation of the organization of cortical and lumbar motor primitives and their roles in improving weight-supported locomotion and stance in spinalized rats. To this end our specific aims are as follows. (1) We will test the hypothesis that the organization of motor representations in S1/M1 trunk area of motor cortex play a crucial role in weight support in rats spinalized at T1O as neonates which receive fetal transplants. (2) We will test the hypothesis that development of specific lumbar spinal cord motor primitives is critical to independent weight support in spinal rats. (3) We will test the hypothesis that improvement in weight support mediated by pharmacological or other transplant interventions is achieved by altering (A) the primitives organized by cortex through descending controls, or (B) the lumbar primitives in spinal cord.
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