Concentration-dependent recruitment of mammalian odorant receptors

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2019

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Abstract

Deciphering natural odor plumes with dynamic changes in odor concentrations presents a common challenge to all animals. A fundamental challenge in studying the organization principles of the olfactory system to encode odor concentration information is the lack of comprehensively identified sets of activated odorant receptors (ORs) across an odorant concentration range inside freely behaving animals. In mammals, this has recently become feasible with high-throughput sequencing-based methods that identify populations of odorant activated ORs in vivo. In this study, we characterized the mouse OR repertoires activated by two odorants, acetophenone (ACT) and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), from 0.01% to 100% (v/v) concentrations. We also investigated the OR repertoires for structural derivatives of TMT (component of fox odor) such as 2­methyl-2-thiazoline (2MT) and 2,4,5-Trimethylthiazole (nTMT) and 2-sec-butyl-4,5-dihydrothiazole (SBT) for 1% and 100% (v/v) concentrations. We used a combination of in vivo, in situ and in silico approaches to investigate ORs with distinct sensitivities to the tested odorants. We examined Olfr923, which we identified to be one of the most sensitive ACT ORs based on our pS6-IP-Seq data. Using a mouse line that genetically labels Olfr923 positive axons, we provide evidence that ACT activates the Olfr923 glomerulus in the olfactory bulb. This study sheds light on the active process in which unique OR repertoires may collectively facilitate the discrimination of odorant concentrations. Together, these odorant receptors may shape the dynamic aspects of olfactory sensitivity and facilitate odorant intensity coding.

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Hu, Xiaoyang Serene (2019). Concentration-dependent recruitment of mammalian odorant receptors. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/19889.

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