Our laboratory has used assays of the gross behavior of the fruit fly, Drosophila melanogaster, to isolate mutants that alter the sensitivity of the animal to general anesthetics. To narrow the focus of this research toward mutants that directly influence anesthetic targets, we study the neural pathway involved in the visual escape response (VER) of Drosophila, which has the desired combination of simplicity and sensitivity to anesthetic agents. The placement of electrodes that activate the anesthetic-sensitive pathway indicates that the critical target lies in an oligosynaptic pathway that connects the lamina of the visual system with the giant fiber neuron in the deutocerebrum. Mutants that affect the sensitivity of this oligosynaptic pathway will be vital tools for exploring what regulates the sensitivity of the anesthetic target. We are using a minichromosome, Df(1;f)LJ9, to fashion a proper comparison between wild-type flies and those that carry a mutation in a novel locus, harA, that alters halothane sensitivity in behavioral assays. We have also undertaken the cloning of this locus. Genomic clones that cover over 200 kbp from its presumptive location have been obtained; mapping of deficiency breakpoints within these clones has confirmed and refined the position of the gene.
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