Development of Innervation Topography in Muscle
Motoneurons project onto muscles in an orderly topographic manner.We have made a detailed mapping of these projections in two musclesof the rat, the anterior serratus and the diaphragm. Ourobservation that topographic cues may precede synapse eliminationsuggests that major factors responsible for topography may occurprior to birth. We have also observed that after the nerve toeither of these muscles is transected, selective reinnervationoccurs, and this reinnervation is even more specific when performedin neonates. We propose to study some of the developmentalmechanisms that might account for this topography in both normaland denervated neonatal rats. The proposed experiments aredesigned to answer three general questions. Firstly, does atopographic bias exist during late prenatal and early postnataldevelopment? Intracellular electrophysiological techniques willbe used to estimate the topographic projection of the motor poolonto the diaphragm or serratus during development. Parallelmorphological studies will be carried out at each postnatal timeperiod. Secondly, do neonatal motoneurons reinnervate their muscletargets in a topographically specific manner? Our observations ofselective reinnervation of neonatal muscles will be extended toinclude the effects of denervation during the period of synapseelimination and the long term synaptic rearrangement followingreinnervation. We will also test the specificity of reinnervationunder conditions favoring axonal sprouting. We will also assesschanges in axonal clustering using fluorescence- histochemicaltechniques. Thirdly, what changes occur in the organization of themotor column during postnatal development and after selectivereinnervation of neonatal muscles? We will estimate the spatiallimits of the motor column, and using retrograde fluorescenttracers we will assess the changes in its organization duringdevelopment and following reinnervation. The unique contributionthis proposal offers is that it will focus on emergent topographyin two well characterized and highly ordered muscles under twoconditions: normal development and selective reinnervation.Results from these studies will help to clarify when orderedtopography emerges during development, and how it is affected bysynapse elimination and reinnervation. These studies have thepotential to open up an important area of research focusing onearly developmental cues for topographic innervation.