The general aims of this project are to study the factors controlling the numerical and qualitative composition of photoreceptor synapses that form in the first neuropile, or lamina, of the optic lobe of the flies Drosophila and Musca. The modules of this neuropile, called cartridges, comprise small, fixed numbers of identified neurons, which we will sample using quantitative single-section EM to estimate synaptic frequencies, measure synaptic contact sites and cell surface areas; and serial EM to trace out synaptic connections between elements, and undertake computer 3-D reconstructions of cell morphologies. Based on our previous analysis of normal synaptogenesis, we especially want to understand the control of the developmental assembly of multiple-contact synapses (dyads, triads, etc.), for which the fly receptor tetrad synapses are a model. Cross-species transplant experiments designed to allow hybrid synaptogenesis will test the conservation of synaptogenetic signals between homologous neurons in different species. The mutant Vam will procure the loss of one element of the postsynaptic tetrad through its spontaneous degeneration, allowing other cells the opportunity to replace it, so revealing their synaptogenetic preferences. We will explore a second mutant, nonC, for abnormal connections with respect to our previous wild-type descriptions, as the first analysis of visual connectivity mutants. Quantitative synaptogenesis will be examined in the mutant gigas, to examine the causal influence of cell enlargement on synaptic frequency. Complete EM series of the cartridge will be used to assess the ratio of synaptic reciprocity between cells sharing afferent and feedback synapses, in the face of size-induced variations in synaptic frequencies. Dynamic aspects of adult synapses will be examined during synaptic loss following degeneration of photo-ablated receptor terminals, and during normal synaptic turnover in the lamina. The connections of lamina cell terminals in the second optic neuropile will also be explored to complete the synaptic inventory of these cells, thereby furthering our understanding of the circuits susceptible to genetic lesions in visual mutants. The studies proposed here, because they aim to produce a basic model of synaptogenesis applicable to multiple-contact synapses, such as the dyads and triads found widely in visual systems, should contribute to a general understanding of the perturbations in disease states to which visual synapses are susceptible during their growth and development.
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