Molecular Mechanisms Of Nociception PDF Download

In order to survive, an organism must be able to sense its surroundings. One particularly important sense is the processes of nociception, the ability to detect noxious stimuli. In Drosophila, when a noxious stimulus is sensed, larvae will perform a distinct rolling behavior. It is valuable to investigate the molecular mechanisms that give rise to the Drosophila larva's ability to sense noxious stimuli and to produce nociceptive rolling behavior as this will allow for a greater understanding of the nociceptive neural circuit and further insight into sensory perception. With the strong homology between Drosophila genes and human genes, these studies could find new targets for pain management. The initial focus of this dissertation was the gene defective proboscis extension response 11 (dpr11). dpr11 is a member of the immunoglobulin superfamily of proteins and it is part of a recently discovered protein network, the Dprome. It was my hypothesis that Dpr11 acts at synapses of nociceptor neurons to direct the formation of connections to downstream secondary neurons. While dpr11 was not found necessary for nociceptive behavior in Drosophila, gene expression studies supported the hypothesis that dpr11 and its binding partners DIP-gamma and DIP-beta are expressed in the nociception circuit. Importantly, dpr11-RNAi tests confirmed an off-target effect on another gene paralytic. Paralytic codes for the only voltage-gated sodium channel in Drosophila, and it is highly processed with many alternative transcripts. This study presents evidence that there are novel isoforms of para that may have a role in thermal nociception. This is a unique finding that relates to pain mechanisms in vertebrates as para is homologous to human voltage-gated sodium channels that are implicated in pain processing. This dissertation will also touch on TRP channels involved in sensory processing, including a mechanotransduction channel nompC and dTRPA1, the Drosophila homolog of human TRPA1. Data present a model for a novel role for nompC in the glia of the Drosophila larval brain, and information on the regulation of dTRPA1 in Drosophila nociceptive neurons. In summary, this dissertation broadly investigates the genetics behind neural circuit formation and sensory transduction processes, lending insight into how genes contribute to behavior and adding important information to the field of pain processing.