Return to search

Modulators of Ion Channels Crucial to Rodent Olfaction

Olfaction allows vertebrates to sense their chemical environment, and plays an important role in feeding behavior, reproduction, memory and learning. The first portion of the dissertation examined the signal transduction cascade in the rodent vomeronasal organ (VNO). The proteins in this cascade have been individually well-characterized over the last 20 years; however, little attention has been paid to the role of protein-protein interactions among these molecules. I found two novel binding partners for the transient receptor potential 2 channel (TRPC2), which establishes the first electrical signal in the pheromone transduction pathway, in the native VNO. Homer 1b/c was found to co-immunoprecipitate with TRPC2 and the inositol trisphosphate receptor (IP3R) from rat VNO lysates. The second new protein partner was chaperone with previously no known function in the VNOs. Receptor transporting protein 1 (RTP1) expression was investigated with immunohistochemical techniques and was localized to to the VNO sensory epithelium. RTP1 also co-immunoprecipitated with TRPC2 from rat VNO lysates and, additionally, RTP1 increased TRPC2 surface expression as measured by cell-surface biotinylation. When co-expressed with RTP1 in human embryonic kidney cells, TRPC2 formed a functional channel as measured with whole-cell electrophysiology. The second portion of this dissertation is a commentary on the function and importance of the VNO in human mate selection. The published literature on human vomeronasal function is briefly examined. With this in mind, I concluded that VNO has no role in human behavior. The last portion of this doctoral dissertation examined the role of brain-derived neurotrophic factor (BDNF) in the mouse olfactory bulb (OB). Mitral cells, the principle output cells of the OB, express tyrosine receptor kinase B (TrkB) the high-affinity BDNF receptor. OB interneurons express the low-affinity BDNF receptor, p75NTR. Following naris-occlusion more mitral cells became immunoreactive and interneurons became less BDNF immunoreactive. In the OB, only the unprocessed proBDNF was detected with immunoblot. In a slice preparation, proBDNF did not alter mitral cell excitability while mature BDNF did. Interestingly, intranasal delivery of proBDNF, but not BDNF, induced activated-caspase 3 immunoreactivity in OB interneurons and reduced tyrosine hydroxylase immunoreactivity. Thus, BDNF modulates mitral cell excitability and proBDNF modulates interneuron markers of cell death. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2011. / July 15, 2011. / brain-derived neurotrophic factor, mitral, olfaction, transient receptor potential channel, vomeronasal / Includes bibliographical references. / Debra Ann Fadool, Professor Directing Dissertation; Choogon Lee, University Representative; Wu-Min Deng, Committee Member; Frank Johnson, Committee Member; Michael Meredith, Committee Member.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_183003
ContributorsMast, Thomas G. (authoraut), Fadool, Debra Ann (professor directing dissertation), Lee, Choogon (university representative), Deng, Wu-Min (committee member), Johnson, Frank (committee member), Meredith, Michael (committee member), Department of Biological Science (degree granting department), Florida State University (degree granting institution)
PublisherFlorida State University, Florida State University
Source SetsFlorida State University
LanguageEnglish, English
Detected LanguageEnglish
TypeText, text
Format1 online resource, computer, application/pdf
RightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them.

Page generated in 0.002 seconds