The objectives are to study the inductive relationship between developing central and peripheral synapses, and the influence of these synapses on development changes in motoneuron properties. To ensure specific and long-term interaction between cells, differentiation of synapses is directed by gene expression as well as by influential signals passing in both directions across the synapse. Detailed information has accumulated describing the function of sensory-motor connection in adult vertebrates, but little is known about their development. Most knowledge comes from studies of developing central synapses in invertebrates, and non-mammalian vertebrates such as tadpole and chick. I will study the electrical and pharmacological properties of immature motoneurons in rat embryos, and investigate the roles of developing primary afferent-motoneruon contacts and peripheral nerve-muscle interactions on these properties. I shall study pattern and time course of development of spinal reflexes and the initial specificity of afferent-motoneuron contacts. Studies will be carried out in vitro, using isolated segments of thoracic spinal cord with or without their adjacent intercostal muscles. The small size of the embryonic spinal cord allows adequate penetration of oxygen and nutrients into the tissue. The advantages of using spinal cord-intercostal muscle explants are: 1) motoneurons are cultured in continuity with the muscles they normally innervate in vivo, and 2) we have previously described the chronology changes that occur during development of intercostal nerve-muscle contacts in vivo and in organ culture, and thus will be able to correlate these changes with the differentiation of motoneurons that innervate them. Maintaining these explants in the controlled environment of organ culture is valuable for isolating signals that influence motoneuron properties and the formation of central neuronal interactions. To broaden our knowledge about the way functional neuronal circuits develop, we must extend our information about the mechanisms involved in specificity of synapses during development. Such an understanding may give insight into mechanisms of long-term interactions between cells and reasons for their inability to re-establish these interaction following lesions in the central nervous system.
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