The goal of this project is to understand the assembly of the nervous system at the single cell level. Our strategy is to study the neurons of simple organisms in order to understand phenomena found throughout the animal kingdom, including man. The wiring diagrams of the brains of all animals are assembled in two major steps. One step is to assign neurons to particular classes which, in turn, determines a set of synaptic connections. This is usually called chemoaffinity. A second step is the sharpening of this basic blueprint by competitive interactions. Presynaptic cells compete for synaptic territory on the postsynaptic cell and thereby optimize the match between pre- and postsynaptic cells. We are interested in the mechanisms underlying these two steps in circuit assembly and will study them in the simple nervous systems of insects. The proposal will use standard electrophysiological techniques as well as genetic analyses. First, we will examine the synapse between two identified neurons to assess whether there is a correlate between structure and the quantal release characteristics at this synapse. We will then test the hypothesis that the position at the time of a neuron's last mitosis is translated into a blueprint for connectivity. A second group of experiments will begin a genetic analysis of chemoaffinity and competition. The fruitfly, Drosophila, will be used to begin searching for mutations which alter neural connectivity. These genetic studies should reveal genes which are important to the assembly of the brain. Ultimately, we would hope to be able to understand the molecular events involved in producing specific synaptic connections.
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