SYNAPSE FORMATION AND GROWTH IN AN AUTONOMIC GANGLION

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The long-range objective of my research is to understand the mechanisms that underlie the formation of synapses between neurons during embryogenesis. The specific objectives of this proposal are 1) to complete an analysis of synaptic growth in the cardiac ganglion of postmetamorphic Xenopus laevis and 2) to study the initial formation and the growth of synapses on developing cardiac ganglion cells in larval animals. In mature animals the innervation of individual neurons is dominated by a preganglionic axon which supplies all the synaptic boutons found on the ganglion cell body. During postmetamorphic life the total area of synaptic contact grows by an increase in bouton number, and the increase in bouton number is exactly matched by an increase in ganglion cell size. By studying transmitter release from the principal synaptic input to ganglion cells and by counting boutons on physiologically characterized cells, we shall determine whether boutons represent equivalent amounts of transmitter release and whether they represent the functional unit of synaptic growth. By studying the innervation of both diploid and larger tetraploid ganglion cells in chimeric animals, we hope to determine the basis of the compensatory growth of cell size and bouton number in postmetamorphic animals. The arrival of preganglionic axons in the developing cardiac ganglion will be visualized by filling techniques, and nascent synapses will be studied both anatomically and physiologically. How do the structure and release properties of newly formed boutons compare with those of mature ones? The growth of synapses in larval animals will be analyzed to learn whether boutons are the units of synaptic growth from the very onset of synaptogenesis. Synapse elimination will be investigated by physiological techniques, and we shall ask whether the ganglion cell body is ever innervated by more than one preganglionic axon. Finally, we shall search for transient connections between ganglion cells. Such connections are ordinarily suppressed by preganglionic innervation but may appear early in development. These studies will increase our understanding of how synapses between neurons form and grow during development. They will also identify the stages when the process of synapse formation may go awry.