Rescuing transient corticospinal terminations and promoting growth with corticospinal stimulation in kittens

Development of corticospinal (CS) terminations is activity dependent. In the cat, activity-dependent refinement of termination topography occurs between weeks 3 and 6. Initially, sparse terminals are present in the gray matter bilaterally, including the motor nuclei. By week 6, virtually all motor nuclear terminations are eliminated, as are most ipsilateral terminations. In this study, we determined whether electrical stimulation of CS axons could be used to rescue transient terminations and promote their growth. We implanted microwires in the pyramid or spinal white matter to stimulate CS axons (2 hr/d, 330 Hz, 45 msec burst, 2 sec intervals) for 2-3 weeks during the refinement period. CS terminations were traced using wheat germ agglutinin conjugated to horseradish peroxidase. Animals were killed after week 6. Stimulation produced dense terminations bilaterally, including within the motor nuclei. Termination density was least in lamina 1 and ventral lamina 9. Reticular formation stimulation produced a control (i.e., nonstimulated) termination pattern. To determine whether CS stimulation affected development of the nonstimulated CS system, we traced terminations from the contralateral cortex using biotinylated dextran amine. Compared with controls or after reticular formation stimulation, there was a shift in the distribution of terminations of the nonstimulated side to more dorsal laminas, which is where the stimulated CS system had fewer terminals. This distribution shift is consistent with competition for termination space between the CS systems on both sides. Our findings indicate that activity can be harnessed to bias CS axon terminal development. This has important implications for using activity to modify motor system organization after perinatal CNS trauma.