Harnessing activity-dependent plasticity in the developing corticospinal system to restore motor function after perinatal brain injury

Abstract

The corticospinal tract (CST) is the principal motor control pathway for skilled movements. The CST, as well as the motor behaviors that it is important for controlling, has a protracted postnatal development in humans and many animals. We first discuss our experiments in the cat, showing that CST neuronal activity is important for normal development of the tract; especially for development of the proper pattern of connections between CST axons and neurons in spinal cord motor circuits. We compare our results in the cat using neural pathway tracing techniques with research on development of the CST in humans using transcranial magnetic stimulation, showing that the cat model captures key features of normal human CST development. In the human, damage to the CST during development produces cerebral palsy, a debilitating motor control disorder. Cerebral palsy research suggests that the motor signs of this condition reflect both the loss of development of a strong contralateral CST, together with development of aberrant dense ipsilateral connections between the CST and spinal motor circuits. We have developed a cat model of unilateral (i.e., hemiplegic) cerebral palsy that both captures these key defects in CST connections and exhibits motor control impairments. We discuss our work, showing that harnessing activity-dependent processes later in development is capable of both restoring the proper connections of the CST in this model and restoring normal motor function.