The long-term objective of this proposal is to understand how genes specify the structure, functioning and development of a behavioral network. Toward this end, the anatomically simple egg-laying system of the nematode Caenorhabditis elegans will be analyzed. Mutants abnormal in egg laying will be used to define both the neurons that function in egg laying and the genes that specify the development of those neurons. The functional roles of neurons implicated in egg laying by anatomical and/or genetical studies will be tested by surgically removing those neurons using a laser microbeam. In these ways it should be possible to elucidate the complete neural circuit responsible for controlling egg laying, from the chemosensory neurons in the head to the serotoninergic HSN motor neurons that innervate the vulval and uterine muscles and drive egg laying. These studies should reveal how the nervous system responds to information in the environment to control not only egg laying but also feeding behavior, defecation and locomotion, all of which are coordinately regulated with egg laying. Thus, this project should provide novel insights concerning information processing by a nervous system, i.e. how a neural circuit senses and integrates multiple sensory inputs to bring about an appropriate army of behavioral responses. Detailed genetic and molecular genetic studies of genes that affect the HSN motor neurons should reveal molecular mechanisms responsible for specific HSN characteristics, including cell migration, axonal outgrowth, neurotransmitter expression and synapse formation. This information should increase our understanding of how the complexity of the nervous system is specified by the genome. Knowledge of how genes specify the development and functioning of the nervous system as well as of how mutations cause nervous system dysfunction could lead to the understanding and cure of various human neurological disorders. In addition, information gained from these studies concerning nematode behavior and neurobiology could help in the prevention and/or treatment of diseases caused by parasitic nematodes, which are a major source of human suffering in the world today.
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