Motoneurons project onto muscles in an orderly topographic manner. We have made a detailed mapping of these projections in two muscles of the rat, the anterior serratus and the diaphragm. Our observation that topographic cues may precede synapse elimination suggests that major factors responsible for topography may occur prior to birth. We have also observed that after the nerve to either of these muscles is transected, selective reinnervation occurs, and this reinnervation is even more specific when performed in neonates. We propose to study some of the developmental mechanisms that might account for this topography in both normal and denervated neonatal rats. The proposed experiments are designed to answer three general questions. Firstly, does a topographic bias exist during late prenatal and early postnatal development? Intracellular electrophysiological techniques will be used to estimate the topographic projection of the motor pool onto the diaphragm or serratus during development. Parallel morphological studies will be carried out at each postnatal time period. Secondly, do neonatal motoneurons reinnervate their muscle targets in a topographically specific manner? Our observations of selective reinnervation of neonatal muscles will be extended to include the effects of denervation during the period of synapse elimination and the long term synaptic rearrangement following reinnervation. We will also test the specificity of reinnervation under conditions favoring axonal sprouting. We will also assess changes in axonal clustering using fluorescence- histochemical techniques. Thirdly, what changes occur in the organization of the motor column during postnatal development and after selective reinnervation of neonatal muscles? We will estimate the spatial limits of the motor column, and using retrograde fluorescent tracers we will assess the changes in its organization during development and following reinnervation. The unique contribution this proposal offers is that it will focus on emergent topography in two well characterized and highly ordered muscles under two conditions: normal development and selective reinnervation. Results from these studies will help to clarify when ordered topography emerges during development, and how it is affected by synapse elimination and reinnervation. These studies have the potential to open up an important area of research focusing on early developmental cues for topographic innervation.
