Remodeling of synaptic structures in the motor cortex following spinal cord injury

Spinal cord injury (SCI) results in a severe and permanent loss of motor function. Although regeneration of severed axons is extremely limited, spared motor system undergoes a substantial extent of structural remodeling, contributing to a spontaneous recovery of motor function. Potential mechanisms of the structural plasticity occurring in the motor system including the motor cortex are not fully understood. In this dissertation research, I tested a hypothesis that SCI leads to a remodeling of synaptic structures in the motor cortex. Confocal microscopic imaging demonstrated time-dependent changes in density of postsynaptic spine structures in the motor cortex after SCI. Detailed analysis of morphology showed that dendritic spines are more elongated along with increased frequency of filopodium-like long dendritic protrusions, suggesting a more immature pattern of synaptic structures after SCI. Immunoblot analysis of synapse-associated proteins in the motor cortex suggested that the adhesion between pre- and postsynaptic membranes is attenuated in parallel with the spine remodeling with a time scale ranging from days to weeks. Exposure to enriched housing, a well established intervention to improve motor recovery, increased the complexity of motor cortical network by adding more dendritic spines. The environmental modification largely abolished the SCI-induced alteration in spine length and head diameter. However, dendritic spines in the motor cortex had still elongated, slender morphology after SCI with enriched housing alone. Transplantation of embryonic spinal cord tissue and intrathecal NT-3, which previously have been demonstrated to support functional recovery and axonal sprouting, almost completely restored the pre-injury pattern of spine morphology when combined with enriched housing. These results suggest that (1) SCI leads to dynamic remodeling of dendritic spines in the motor cortex with days' to weeks' time scale, (2) dendritic spines change their morphology in response to a decrease in activity by SCI and enhanced activity by enriched housing, (3) combinatorial treatment with transplantation of embryonic spinal cord tissue and intrathecal NT-3 can potentiate the effects of enriched housing on spine remodeling. This dissertation research further suggests that modulation of the synaptic remodeling in the motor cortex may be a promising strategy to enhance functional recovery after SCI.