Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: model validation and behavioral effects

Introduction: Unilateral brain injury in neonates results in largely contralateral hand function impairment in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. In this study, we first developed a model of sensory tract injury in neonatal rats by targeting the thalamocortical tract, and then we used this model to assess the effects of sensory lesions on paw use. Methods: In the postnatal day 7 rats, we used three types of lesions to the thalamocortical tract: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. Results: Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the thalamocortical tract, while sparing the adjacent corticospinal tract in the internal capsule. Given that electrolytic lesions were the most specific and sensitive for targeting the thalamocortical tract, this model was used for behavioral experiments to measure the impact of sensory tract lesion on dexterity. The cylinder exploration and pasta handling tests were used to test the changes of forelimb use at 8 weeks after electrolytic lesion when the rats reached maturity. Lesions to the thalamocortical tract were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury. Conclusion: Overall, specific sensory system lesions of the thalamocortical tract impair forelimb use, suggesting a key role for skilled movement.