Published: 2014
Total Pages: 0
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A complete understanding of how behavior is controlled by the nervous system must include detailed knowledge of the underlying circuitry and neurochemistry. The parasitic nematode Ascaris suum, with only 298 neurons, is an exceptionally well-suited system in which to obtain this level of detail. Whereas a great deal of the cytoarchitecture, electrophysiological properties, and classical transmitter phenotypes of individual cells has been described, much is still unknown about the great diversity of modulatory neuropeptides. A description of their structure and activity is essential for understanding the in the control of behavior. In this thesis, we use a combination of mass spectrometry (MS), bioinformatics, and molecular biology to discover and localize neuropeptides in the motor nervous system. The peptides are then chemically synthesized and tested for bioactivity. Direct profiling of single neurons by matrix assisted laser desorption/ ionization time-of-flight (MALDI-TOF) MS identified diverse and interesting patterns of peptide expression. In parts one and two, we targeted ventral cord motorneurons that innervate the somatic body wall musculature responsible for locomotion. In the cholinergic excitatory motorneurons, two different peptide expression profiles were observed. The first was found in neurons responsible for forward locomotion, and the second, a completely different set of peptides, was present in neurons responsible for backwards locomotion. Aside from confirming the identity of previously known peptides, all of which had been shown to be bioactive, we also identified six novel peptides. In the second part, in the GABAergic inhibitory motorneurons we found a novel bioactive peptide with potent inhibitory effects on muscle contraction. In the third part, we mapped peptide expression in the 4 GABAergic RME ring motorneurons neurons of the head. The peptides in these neurons, of which 7 were novel, were different from those in the ventral cord inhibitors. Three peptides encoded by one of the transcripts had inhibitory effects on muscle contraction. This is the first study to identify peptide expression patterns in the motor neurons. In this study we have not only found novel peptides but also identified the peptides that are likely to be most relevant to locomotion in A. suum.