The hamster pyramidal tract arising from the sensorimotor cortex innervates all segments of the spinal cord, and develops entirely postnatally. When axons in the medullary pyramid are severed early in development, pyramidal tract axons regrow, establish appropriate synapses in the cervical spinal cord and thus preserve fine motor control of the forelimb. In order to compare normal development of a CNS pathway with CNS axons regenerating after injury, the developing and regenerating hamster pyramidal tract will be studied with respect to neuronal topography, axon guidance, growth associated proteins, morphology of axon arborizations, and development of motor behavior. Development of topography in corticospinal neurons will be mapped by retrograde double labeling with fluorescent dyes. Growing pyramidal tract axons in the decussation will be labeled with HRP and their relationship to non-neuronal processes in the cellular environment examined with light and electron microscopy. During development, putative glial guides at the decussation will be characterized ultrastructurally and with immunocytochemical localization of cell-specific antisera to cytoskeletal elements to establish their glial identity and to follow changes in their filament proteins as pyramidal fibers grow into the region. Rapidly transported membrane proteins, designated growth associated proteins (GAPs), will be analyzed with gel electrophoresis to determine whether GAPs represent a discrete set of proteins whose expression is characteristic of neurons during axonal outgrowth in the developing and regenerating CNS. Branching patterns characteristic of developing, mature and regenerating axon arbors will be described morphologically by labeling axons with HRP in vitro slice preparations. The emergence of specific behaviors requiring sensorimotor integration will be correlated with development of corticospinal axons. Filmed behavior of hamsters with infant lesions of the pyramidal tract will be analyzed to measure the ability or regenerating axons to preserve the normal development of speed, strength and accuracy of specific motor behaviors.
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