Interaction of spontaneous retinal activity and semaphorin signaling on stereotyped axon pruning in primary visual cortex

Proper functioning of the nervous system is dependent on the establishment of a precise pattern of neuronal connectivity. Functional connectivity can largely be credited to a period of early development when initially formed exuberant neuronal connections are pruned back to eliminate inappropriate contacts. Trimming immature connections promotes a more precise and functional network. Stereotyped axon pruning is a widespread phenomenon that refines neuronal contacts in the neuromuscular junction, as well as the hippocampus and corticospinal tract (CST). Although essential during development, the mechanism of axon pruning remains unresolved. In the visual system, axons originating from layer V pyramidal neurons initially target the spinal cord but are subsequently pruned back to the brainstem. Prior evidence indicates that the semaphorin family of axon guidance molecules, and their cognate neuropilin and plexin receptors, mediate this pruning. In addition, we recently found that pruning of CST axons is dependent on patterned spontaneous activity in the retina. Whether or not these mechanisms operate along the same or separate (independent) signaling pathways has not been addressed. Here, we elucidate the interaction between these pruning mechanisms and their combined effect on remodeling of CST axons. Using mutant mice enucleated at birth and in vivo tracing experiments, we will examine the effect of combined deficits on visual cortex CST pruning. Based on previous work, we predict no difference in pruning deficits when both mechanisms are inactivated compared with previous results using independent inactivation. This would support our hypothesis that these pruning mechanisms operate along the same pathway.