Olfactory perception affects the food choice of most living species. A strong set of data have been accumulated to demonstrate that the olfactory bulb, the first relay of olfactory information, as a metabolic sensor. Mitral cells of the olfactory bulb project to central processing areas such as the piriform cortex. Our laboratory has recently determined that a subpopulation of mitral cells can modulate their firing frequency in response to changes in extracellular glucose concentration, thus acting as glucose sensors. Glucose sensors are found throughout the brain in the hypothalamus, the brainstem, amygdala, septum and hippocampus. Glucose has been extensively studied in non-neuronal tissues given its essential role as the main cellular fuel. In glucose sensing neurons, however, where glucose acts as a signal, this process remains largely unknown. My dissertation project focused on providing further evidence of glucose-sensing in the olfactory system, specifically the olfactory bulb and the anterior piriform cortex. I hypothesized that glucose-sensing happened via the insulin-dependent glucose transporter type 4. I first mapped the presence of the glucose transporter type 4 in the different cellular layers of the olfactory bulb and the piriform cortex. mRNA of the glucose transporter type 4 and the voltage-gated potassium channel Kv1.3 were present in the mitral cell layer of the olfactory bulb. In the piriform cortex, the glucose transporter type 4, Kv1.3, and insulin receptors exhibited a broad diversity of distribution. Neurons in the different layers of the piriform cortex expressed one of the three proteins, two of them, or the three proteins co-expressed together. Both mitral cells in the olfactory bulb and pyramidal neurons in the piriform cortex had glucose-sensing properties whereby glucose modulated the electrical behavior of these cells. Mitral cells increased or decreased their firing frequency in response to low glucose (1 mM) while the electrical activity of pyramidal neurons was dependent on extracellular glucose concentration. Switching glucose concentration from high (10 mM) to low (0.5 mM) decreased the instantaneous frequency in pyramidal neurons. Switching glucose concentration from moderate (5 mM) to low (1 mM) revealed two subpopulations of pyramidal neurons that either decreased their instantaneous frequency or were unresponsive to the change in glucose concentration. Pyramidal neurons were responsive to insulin as well, and both mitral cells and pyramidal neurons required glucose metabolism to sense glucose as demonstrated in vitro by using the glucose analog 2-deoxyglucose, or alloxan, a glucokinase inhibitor. Furthermore, I bilaterally implanted cannulas into the anterior piriform cortex of rats, micro-injected insulin (172 nM), glucose (10 nM), or a small peptide Kv1.3 inhibitor margatoxin (0.1 nM). Animals were then subjected to an olfactory habituation/dishabituation paradigm. Results showed that insulin and glucose reduced olfactory discrimination but blocking Kv1.3 improved olfactory habituation and discrimination. My work is the first to demonstrate the presence of the glucose transporter type 4 in the anterior piriform cortex, it is also the first to provide insights into the glucose sensing transduction cascade in the olfactory system, a process that appears to be modulated by insulin and glucose metabolites. The results of this study help provide a better fundamental understanding of the physiological regulation of olfactory perception in relationship with the metabolic status. This study might also pave the way towards identifying a potential therapeutic target to control overeating; a main cause of obesity in western countries. / A Dissertation submitted to the Program in Neuroscience in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2018. / July 18, 2018. / Food intake, Glucose, Metabolism, Olfactory, Sensing / Includes bibliographical references. / Debra Ann Fadool, Professor Directing Dissertation; Michael Blaber, University Representative; Michael Meredith, Committee Member; Thomas C. S. Keller, Committee Member; Michael Overton, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_655818 |
| Contributors | Al Koborssy, Dolly (author), Fadool, Debra Ann (professor directing dissertation), Blaber, Michael (university representative), Meredith, Michael (committee member), Keller, Thomas C. S. (committee member), Overton, J. Michael (committee member), Florida State University (degree granting institution), College of Arts and Sciences (degree granting college), Department of Biological Science (degree granting departmentdgg) |
| Publisher | Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text, doctoral thesis |
| Format | 1 online resource (231 pages), computer, application/pdf |
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