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Characterization of a novel population of olfactory sensory neurons in the main olfactory epithelium

Final Report Summary - MOUSEOLF (Characterization of a novel population of olfactory sensory neurons in the main olfactory epithelium)

Sensory organs allow animals to extract information from their surroundings and to build a representation of the outside world. An appropriate representation of the environment is a prerequisite for an organism to respond adequately to its peers, predators or prey, or to locate food sources and shelter, for example. To achieve this, animals rely on different sensory cues and olfaction is the most important and basic sense for many species, such as rodents.
In mice, the olfactory system can be divided into three subsystems that are physically separated within the olfactory cavity: the main olfactory epithelium (MOE), the vomeronasal organ (VNO) and the Grueneberg ganglion. Specialized olfactory sensory neurons (OSNs) populate these olfactory structures. Each OSN expresses one chemosensory receptor type, responsible for detecting specific odors. Axonal projections of neurons expressing the same receptor coalesce into glomeruli in the olfactory bulb, a frontal part of the brain specialized in odor processing. To date, olfactory chemoreceptors are divided into five superfamilies, all of which are G-protein coupled receptors. They consist of the odorant receptors (ORs) (1), the vomeronasal receptors type 1 and 2 (V1Rs and V2Rs) (2-5), the trace amine-associated receptors (TAARs) (6) and the formyl-peptide receptors (FPRs) (7-8).

Recently, our group identified a novel population of olfactory neurons in the MOE, that represents approximately 1% of the complete neuronal population of the MOE. This subset of neurons has the particularity of expressing a protein called TrpC2, an ion channel that is typically part of the VNO transduction cascade and that was thought to be absent from the MOE. Given the striking phenotypes that TrpC2-deficient mice exhibit (phenotypes attributed to VNO malfunction), the presence of this channel outside the VNO is critical. These phenotypes include male-typical mounting behavior by mutant females and male-mounting by mutant males(9-11). Our aim was thus to further characterize this population located outside the vomeronasal organ, and in particular to identify the olfactory receptor(s) it expresses. To this aim, we used a transgenic approach that specifically labeled this TrpC2+ population with a fluorescent marker.
We found that TrpC2 + neurons from the main olfactory epithelium project to the dorso-frontal olfactory bulb into approximately 50 glomeruli. In addition, four large glomeruli, on the ventro-caudal side of the olfactory bulb were also targeted by TrpC2 neurons.
We isolated neurons expressing TrpC2 in the MOE by fluorescence-activated cell sorting (FACS) and performed RNA deep sequencing. In parallel, we used two additional strategies. The first one used a subtractive approach to identify receptors in the TrpC2 population using whole MOEs where this population was genetically ablated (and comparing its transcriptome to that of wild-type MOEs). The second involved the physical extraction of the fluorescent TrpC2+ ventral glomeruli, followed by RNA deep sequencing. We identified specific odorant receptor gene candidates. These are currently being genetically deleted in order to evaluate the role played by this non-vomeronasal TrpC2+ olfactory sensory population.

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