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[Erscheinungsort nicht ermittelbar]: eScholarship, University of California, 2006
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Hochschulschrift:
Dissertation, eScholarship, University of California, 2006
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Beschreibung:
One of the main goals of neurobiology, and the focus of this dissertation, is to understand how genes act within a nervous system to generate behavior. The nematode Caenorhabditis elegans has a relatively simple nervous system comprised of 302 neurons with known connectivity. Despite this simplicity, C. elegans displays a wide-range of behaviors with surprising complexity. Well-developed genetics combined with a manageable nervous system make C. elegans a useful model to study how genes alter behavior. This dissertation focuses on the mechanosensory neurons of C. elegans. In the development of the gentle touch mechanosensory neurons, serotonin appears to act as permissive cue that allows these neurons to migrate to their proper locations. Mutations in Go-alpha (goa-1) signaling and the calcium channel (unc-2) also affect migration of the gentle touch neurons. Genetic analysis confirms that these genes act in the same pathway to confer motility to the migrating touch neurons. Dopamine is also important for the gentle touch neurons, but not developmentally. DOP-1, a D1-like dopamine receptor expressed in the touch neurons, is required for normal habituation of the gentle touch response. Cell-specific rescue confirms a role for DOP-1 signaling in the touch cells during habituation. Further genetic analysis indicates that Gq-alpha (egl-30) signaling couples to DOP- 1. This signaling utilizes the second messengers IP3 and DAG to act on ER calcium and PKC activity respectively to modulate habituation. In vivo calcium imaging indicates that this signaling cascade acts cell autonomously to regulate touch cell sensitivity. Food is an essential cue for dopamine modulation of touch habituation; in the absence of food, DOP-1 worms habituate at the same rate as wildtype. Experiments also suggest that worms utilize their dopamine neurons to sense food mechanically, and release dopamine to slow habituation; this is dependent on the TRPN channel TRP-4. Another potential mechanosensitve TRP channel in C. elegans, TRPA-1 was recently identified. This channel is not required for gentle touch, but instead a distinct type of mechanosensation, nose touch and also foraging related behaviors. Cell-specific rescue and in vivo calcium imaging confirmed a direct role for TRPA-1 in nose touch neurons