Cerebral palsy (CP) is caused by a variety of factors that result in brain damage and permanently impair motor control, marked by muscle stiffness and spasticity. Despite the seriousness and prevalence (1 in every 400 births), there have been few advancements in therapeutics in recent decades, with most treatments focusing on symptoms after they emerge rather than prevention and reduction of damage. This may be due to the historic lack of an animal model that displays a prominent CP-like phenotype in which it is possible to study the specific mechanisms giving rise to motor impairments. In this project, we propose parallel longitudinal studies in children with CP and in a new, clinically relevant animal model of CP. Rabbits subjected to prenatal hypoxia- ischemia (HI) show clear motor symptoms of spasticity associated with CP, most notably muscle stiffness in the limbs, hypertonia and hyperreflexia. Our main goal is to exploit this animal model to directly investigate perturbations in the normal development of spinal neurons and neuronal circuits, while relating cellular changes to motor behavior in both children and young rabbits with and without CP and HI injuries. While damage to the brain and corticospinal tracts have been the focus of much previous research, aberrant development of spinal circuits in CP provides a more accessible target for treatment and therapy of motor dysfunction. After injuries that can cause CP, we know from previous studies in both rabbit and rodent models that 1) there is altered expression of the Cl- transporter, KCC2 in the brain, and 2) spinal levels of serotonin are increased. Both of these factors are tightly developmentally regulated, and could directly promote sustained MN activity when unregulated: 1) with increasing KCC2 expression during development, inhibitory interneurons in the spinal cord switch from a depolarizing to a hyperpolarizing postsynaptic effect; and 2) development of persistent inward currents (PICs) may alter intrinsic excitability of motoneurons (MNs). PICs increase neuronal excitability and sustain firing, but synaptic inhibition is very effective at turning them off. Hence, with loss of appropriate KCC2 expression, PICs are poised to exert an even greater influence on MN behavior. Our overarching hypothesis is that injuries causing cerebral palsy alter the development of spinal excitability in both children and an animal model, including progressive changes in MN PICs and KCC2 expression, in addition to the damage caused to the brain and the descending projections. Along with the well-documented loss of descending inhibitory tone, enhanced excitability in spinal MNs and reduced efficacy of spinal inhibitory synapses could contribute to hypertonia and spasticity of patients with cerebral palsy and these properties could be targeted for treatment.