We propose to continue examining genetic controls over the synthesis of enzymes related to neural transmitters, particularly acetylcholine. We propose to use the small soil nematode Caenorhabditis elegans because a) it has a simple nervous system with reproducibly identifiable cells, b) the physiological functions and transmitter-synthesizing capacities of many homologous cells are known in the larger nematode Ascaris lumbricoides, c) eight mutations with severe effects on acetylcholine metabolism have already been identified, and d) Caernorhabditis elegans is genetically well suited for isolating new transmitter-related mutations. We propose to continue our analysis of apparent structural gene mutations affecting acetylcholinesterase and choline acetyltransferase, and we propose to use these in the coming year to isolate new structural gene alleles as well as regulatory gene mutations affecting these same enzymes. We also propose to use existing and new mutations to examine the effects produced at synapses by genetic manipulations of neurotransmitter levels.