The Use of PRV-Bartha to Define Premotor Inputs to Lumbar Motoneurons in the Neonatal Spinal Cord of the Mouse

The neonatal mouse has become a model system for studying the locomotor function of the lumbar spinal cord. However, information about the synaptic connectivity within the governing neural network remains scarce. A neurotropic pseudorabies virus (PRV) Bartha has been used to map neuronal connectivity in other parts of the nervous system, due to its ability to travel trans-neuronally. Its use in spinal circuits regulating locomotion has been limited and no study has defined the time course of labelling for neurons known to project monosynaptically to motoneurons.Here we investigated the ability of PRV Bartha, expressing green and/or red fluorescence, to label spinal neurons projecting monosynaptically to motoneurons of two principal hindlimb muscles, the tibialis anterior (TA) and gastrocnemius (GC). As revealed by combined immunocytochemistry and confocal microscopy, 24-32 h after the viral muscle injection the label was restricted to the motoneuron pool while at 32-40 h the fluorescence was seen in interneurons throughout the medial and lateral ventral grey matter. Two classes of ipsilateral interneurons known to project monosynaptically to motoneurons (Renshaw cells and cells of origin of C-terminals) were consistently labeled at 40 h post-injection but also a group in the ventral grey matter contralaterally. Our results suggest that the labeling of last order interneurons occurred 8-12 h after motoneuron labeling and we presume this is the time taken by the virus to cross one synapse, to travel retrogradely and to replicate in the labeled cells.The study establishes the time window for virally-labelling monosynaptic projections to lumbar motoneurons following viral injection into hindlimb muscles. Moreover, it provides a good foundation for intracellular targeting of the labeled neurons in future physiological studies and better understanding the functional organization of the lumbar neural networks

The dependence of spinal cord development on corticospinal input and its significance in understanding and treating spastic cerebral palsy

The final phase of spinal cord development follows the arrival of descending pathways which brings about a reorganisation that allows mature motor behaviours to emerge under the control of higher brain centres. Observations made during typical human development have shown that low threshold stretch reflexes, including excitatory reflexes between agonist and antagonist muscle pairs are a feature of the newborn. However, perinatal lesions of the corticospinal tract can lead to abnormal development of spinal reflexes that includes retention and reinforcement of developmental features that do not emerge in adult stroke victims, even though they also suffer from spasticity. This review describes investigations in animal models into how corticospinal input may drive segmental maturation. It compares their findings with observations made in humans and discusses how therapeutic interventions in cerebral palsy might aim to correct imbalances between descending and segmental inputs, bearing in mind that descending activity may play the crucial role in development. \ua9 2007 Elsevier Ltd. All rights reserved