Abstract

Based on pharmacological studies of chemosensory transduction in transient receptor potential channel M5 (TRPM5) knockout mice it was hypothesized that this channel is involved in transduction for a subset of putative pheromones in mouse olfactory sensory neurons (OSNs). Yet, in the same study an electroolfactogram (EOG) in the mouse olfactory epithelium showed no significant difference in the responses to pheromones (and odors) between wild type and TRPM5 knockout mice. Here we show that the number of OSNs expressing TRPM5 is increased by unilateral naris occlusion. Importantly, EOG experiments show that mice lacking TRPM5 show a decreased response in the occluded epithelia to putative pheromones as opposed to wild type mice that show no change upon unilateral naris occlusion. This evidence indicates that under decreased olfactory sensory input TRPM5 plays a role in mediating putative pheromone transduction. Furthermore, we demonstrate that cyclic nucleotide gated channel A2 knockout (CNGA2-KO) mice that show substantially decreased or absent responses to odors and pheromones also have elevated levels of TRPM5 compared to wild type mice. Taken together, our evidence suggests that TRPM5 plays a role in mediating transduction for putative pheromones under conditions of reduced chemosensory input.

Highlights

  • olfactory sensory neurons (OSNs) express one olfactory receptor type among a repertoire encoded by,1,400 genes [1,2]

  • We found that the occluded side of both the septum and the lateral olfactory epithelium (OE) showed significantly higher expression of GFP compared to the control sides, and the effect was consistent across all animals tested (i; p = 0.02, ii; p = 0.006, iii; p = 0.002, iv; p = 0.007, p value false discovery rate (FDR) corrected, p = 0.05, paired t-test, n = 4)

  • We demonstrated that transient receptor potential channel M5 (TRPM5) expression in OSNs is increased by unilateral naris occlusion and that mice that have CNGA2 genetically deleted show elevated expression of TRPM5

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Summary

Introduction

OSNs express one olfactory receptor type among a repertoire encoded by ,1,400 genes [1,2]. TRPM5-expressing OSNs display a zonal expression pattern, and are abundantly found in the lateral and ventral regions and sparsely represented in the septum in the olfactory epithelium (OE) [16] This distribution may hint at the functional role of TRPM5 as computer-simulated airflow within rat olfactory turbinates suggests that inhaled air travels 10 times slower in the lateral and ventral regions where a number of TRPM5-expressing OSNs are found, when compared to the computer-simulated airflow in the medial regions [19]. This distribution pattern of TRPM5expressing OSNs within the olfactory turbinate suggests two possible roles for TRPM5. Expression of TRPM5 could achieve enhanced chemical stimulus-induced activity in the OSNs that are exposed to lower odorant/pheromone levels in the slow airflow regions of the nasal cavity

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