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| Poster #334 Odor Stimulation Enhances Hypothalamic c-fos Expression in Kv1.3 -/- Mice |
| Martina Compagno1, Saptarsi Mitra2, Debra Ann Fadool1,2,3 1Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, United States 2Department of Biology, Florida State University, Tallahassee, FL, United States 3Program in Neuroscience, Florida State University, Tallahassee, FL, United States |
Due to the well-documented link between olfactory bulb activity and the regulation of metabolism, we utilized Kv1.3-/- mice (KO; voltage-gated potassium channel) to examine altered functional connectivity between the olfactory bulb and hypothalamus. Because KO mice are thin without caloric restriction and resistant to diet-induced obesity, we hypothesized they would have enhanced functional connectivity between these regions. Wildtype (C57BL6/J, WT) and KO mice (n=6/genotype) were stimulated with1 mM isoamyl acetate using a custom olfactometer delivering cyclic stimulation, followed by traditional c-fos immediate-early gene immunolabeling. We report a genotype independent, main effect of odor stimulation in the glomerular layer (2w ANOVA, p = 0.019). Moreover, KO mice had increased odor-evoked c-fos labeling over that of WT in both the mitral cell and granule cell layers (2w ANOVA, MCL: p <0.0001; GCL: p = 0.0002). Brain-wide c-fos activation was mapped (n=3/genotype) using tissue clearing and lightsheet microscopy. Computed 3D c-fos density maps were generated using ClearMap and compared within genotype (Student’s t-test). KO mice exposed to odor showed higher c-fos expression in numerous downstream targets compared to WT mice. C-fos activity was analyzed in several energy-sensing regions of the hypothalamus, including the paraventricular hypothalamus (PVH), the dorsomedial hypothalamus (DMH), and the arcuate hypothalamus (ARH). C-fos activity in the PVH was markedly enhanced in KO mice, yielding an odor-genotype interaction (2w ANOVA, p = 0.025). Our study reveals coactivation between the olfactory bulb and energy regulating regions of the hypothalamus. We conjecture that resistance to diet-induced obesity may be mediated by the PVH; a region known to operate in neuroendocrine function. |