A NEW WAY TO STUDY SPINAL CORD INJURY
December 7th, 2005
First-author Florence Bareyre
To circumvent these limitations, we have developed a new method to selectively and completely label the CST in mice. We used mice in which a yellow fluorescent protein (YFP) accumulates in CST axons in the spinal cord, rendering them visible under appropriate illumination. The method uses mice we previously developed, called "STOP-YFP," in which YFP is expressed only in cells that are treated with an enzyme called "cre." Cre is delivered by mating the STOP-YFP mice to another transgenic line in which cre is selectively expressed in the cortex. We then study the offspring that have both transgenes; in them, YFP is expressed in neurons of the cortex. As the CST is the only direct projection from cortex to spinal cord, this leads to specific, complete labeling of this tract in double transgenic mice, which we call CST-YFP.
Using CST-YFP mice, we found that (1) CST axons extend through the spinal cord earlier in development than previously reported; (2) the CST includes minor subpopulations of fibers that are often spared when the main population is cut; (3) this distinct, little-studied subpopulation of <10% of all CST axons accounts for a vast majority (~90%) of the direct CST input to motor neurons in normal animals; and (4) axons of this minor subpopulation form new synapses on motor neurons following injury to the major population. Together, these results provide new data on the structure and development of an important model system for analysis of spinal cord pathology; document a compensatory reorganization that may contribute to functional recovery following injury; and demonstrate the general utility of CST-YFP mice for spinal cord injury research.