SYNAPTIC TRANSMISSION DURING NEURONAL DIFFERENTIATION

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DESCRIPTION: (Adapted from the Applicant's Abstract.) The broad long-term objective is to determine the role of synaptic transmission on neural differentiation. The investigators will focus on the principal cells of the tangential vestibular nucleus of the chick (mammalian lateral vestibular nucleus). The principal vestibulo-ocular reflexes. Special attention will be paid to the mode of synaptic transmission between the developing principal cells and the synapses formed by the giant fibers of the vestibular nerve, the colossal fibers. During development, the colossal fiber synapse, or spoon ending, undergoes several transitions including forming chemical synapses, then mixed synapses, and finally mainly gap junctions with the principal cells. The high degree of specificity in this connection is unsurpassed in the vertebrate nervous system. The investigators will analyze the onset and development of electrical transmission which has not been done in detail, in spite of its reported occurrence at several sites in the mammalian brain. They will utilize brain slices because the tangential nucleus has a highly organized structure well suited to slice analysis. Intracellular and extracellular recordings will be applied in the tangential nucleus following stimulation of the vestibular ganglion. The membrane and synaptic properties of the principal cells will be defined at times when the spoon synapses exhibit changes. They will identify morphologically the cells and synapses recorded from suing fluorescent dyes and electron microscopy. The analysis at the embryonic age when gap junctions first appear and will repeat the strategy at other critical ages. When normal synaptic transmission between CNS neurons is impaired during prenatal or early postnatal development, the young often suffer diminished intellectual abilities throughout life, as in the case of learning disorders and mental retardation. These studies on developing neurons and synapses may provide a basis for preventive strategies or new treatments for diseases of synaptic transmission. In addition, these studies should contribute to our understanding of how the vestibular system begins to function and the role of functional activity on neuron differentiation and neuron survival.