As the nervous system develops, synaptic connections between nerve cells are initially established in a highly specific manner. These initial contacts can then be modified to a limited extent, increasing their specificity still further. A knowledge of the functional and morphological correlates of synaptic development in the central nervous system is basic to an understanding of how nerve cells originally make and then refine and maintain their proper connections. Synaptic connections in the spinal cord between muscle sensory afferent fibers and motoneurons, connections which form the neuronal basis of the stretch reflex, provide an excellent experimental system for studying this problem at the level of single, functionally identified cells. In the frog's spinal cord, these connections form with a high degree of specificity and undergo only limited modifications thereafter. Vestibular inputs to these same motoneurons are also specific in adult frogs, but the manner in which this specificity develops in unknown. A major aim of this proposal is to compare the development of these two sensory inputs to gain insights into how specific synapses are formed. Sensory fibers in the frog can also regenerate after they are cut in the dorsal root, and they re-innervate motoneurons with a high degree of specificity. A continued study of the factors that influence the amount and specificity of this regeneration could help in achieving specific regeneration in human spinal cord after accidental injury. My objectives during the next five years are as follows: 1) Study the normal development of monosynaptic connections between muscle sensory axons and motoneurons at the level of individual functionally identified cells. 2) Extend these studies to the development of the vestibulospinal input to forelimb motoneurons. 3) Examine the effects of types of lesions on the extent of regeneration of sensory dorsal root axons into the spinal cord.
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