The responses of mammalian spinal axons to an applied DC voltage gradient.

We have imposed a steady, rostrally negative, weak (ca 0.4 mV/mm) voltage gradient across transections of ascending white matter tracts in the adult guinea pig using an implanted stimulator and electrodes for about 1 month. We have evaluated the projections of these axons relative to the transection approximately 2 months postinjury by anterograde transport of injected tetramethylrhodamine-conjugated dextran and the use of an indwelling marker device which locates the plane of the original transection. Tract tracing was accomplished with conventional epifluorescence microscopy and confocal laser microscopy. Sham-treated control spinal cords contained well-filled lateral and dorsal column ascending tracts terminating caudal to the lesion which formed at the level of the hemisection. Electric field-treated spinal cords contained similarly labeled columns of axons that penetrated the lesion within the caudal segment of the spinal cord, branched within it, and in some cases such branches projected across the plane of transection. Ascending axons also passed around the lesion through undamaged parenchyma, branched repeatedly at the plane of the hemisection, and passed into the rostral segment of the spinal cord. Spear-shaped endings typical of growth cones were found at the terminals of these processes which often branched again within the rostral segment. Centrally projecting fibers, their processes, and the overall level of branching in these projections was not observed in our previous studies using high molecular weight horseradish peroxidase tracers.