Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals

Abstract

Olfactory sensory neurons (OSNs) in the main olfactory epithelium respond to environmental odorants. Recent studies reveal that these OSNs also respond to semiochemicals such as pheromones and that main olfactory input modulates animal reproduction, but the transduction mechanism for these chemosignals is not fully understood. Previously, we determined that responses to putative pheromones in the main olfactory system were reduced but not eliminated in mice defective for the canonical cAMP transduction pathway, and we suggested, on the basis of pharmacology, an involvement of phospholipase C. In the present study, we find that a downstream signaling component of the phospholipase C pathway, the transient receptor potential channel M5 (TRPM5), is coexpressed with the cyclic nucleotide-gated channel subunit A2 in a subset of mature OSNs. These neurons project axons primarily to the ventral olfactory bulb, where information from urine and other socially relevant signals is processed. We find that these chemosignals activate a subset of glomeruli targeted by TRPM5-expressing OSNs. Our data indicate that TRPM5-expressing OSNs that project axons to glomeruli in the ventral area of the main olfactory bulb are involved in processing of information from semiochemicals.signal transduction ͉ pheromone ͉ stimulated emission depletion (STED) microscopy T he olfactory system perceives not only odorants that convey information on the environment but also semiochemicals (chemicals involved in animal communication, from the Greek semeion for ''sign''), including pheromones (1-4). A key step in transmission of information is activation of the canonical cAMP signaling pathway by binding of odorants to olfactory receptors, resulting in influx of Ca 2ϩ through a cyclic nucleotide-gated (CNG) channel and subsequent depolarization (5, 6). Targeted disruption of elements of the cAMP pathway, including the CNG channel subunit A2 (CNGA2) (7), the G protein G olf (8), or adenylyl cyclase (AC) III (9), result in severe deficit of odorantevoked responses to many odorants, demonstrating the dominant role of the cAMP pathway.Semiochemicals, such as pheromones, social attractants, and major histocompatibility complex (MHC)-related odorants, signal social and sexual status, genetic makeup, and species identity important for the survival of the individual and the species (1, 10-13). Recent studies indicate that both the main olfactory epithelium (MOE) and olfactory bulbs respond to these chemosignals (14, 15). Consistent with these findings, sensory information from the main olfactory bulb projects to areas in the hypothalamus housing neurons that produce gonadotropinreleasing hormone and plays an important role in reproduction (16,17). Further, a class of chemosensory receptors that recognize social amines found in urine have been identified recently in the MOE (18). Thus, it now is clear that the main olfactory system is involved in detection of semiochemicals and that the cAMP signaling pathway plays an important role in signal transduction f...

Transduction for Pheromones in the Main Olfactory Epithelium Is Mediated by the Ca2+-Activated Channel TRPM5

“…Immunohistochemical data have shown that a subset of OSNs express TRPM5 (transient receptor potential channel M5) in the cilia (Kaske et al, 2007;Lin et al, 2007), and because CNG channel subunit A2 (CNGA2) is likely expressed in these cilia (Lin et al, 2007), these studies suggested, but did not prove, that TRPM5 could be activated by Ca 2ϩ influx through CNGA2 and be involved in pheromone transduction in the MOE. In addition, indirect evidence showing differential inhibition by pharmacological block of adenylyl cyclase III of the electroolfactogram (EOG) response of two putative pheromones 2-heptanaone and 2,5-dimethylpyrazine (DMP) versus two general odorants in controls but not in TRPM5 knockouts suggests that TRPM5 is involved in the transduction of pheromonal responses (Lin et al, 2007). Finally, recent work indicated that TRPM5 likely plays a role in mediating transduction for putative pheromones (Oshimoto et al, 2013).…”

Deletion of voltage‐gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system

“…In other loss of function studies, two key olfactory signal transduction proteins, the CNG channel and the G-protein G olf , were not required for generating synaptic specificity in the olfactory bulb (Belluscio et al, 1998;Lin et al, 2000). In the CNG-null animals, the interpretation that odorant-evoked activity does not influence axonal projections is somewhat muddled by the new finding that these mice are not completely anosmic, as initially reported (Brunet et al, 1996), and respond behaviorally (olfactometer), electrically (electro-oculography [EOG]), and cellularly (cfos activity) quite well to odorants that are classified as pheromone-like compounds (heptanone and 2,3-dimethylpyrazine [DMP]; Lin et al, 2006Lin et al, , 2007.In addition, recent genetic manipulation of stimulatory G protein has demonstrated that cAMP may regulate the expression of axon guidance molecules essential for OR-instructed axonal projections (Imai et al, 2006). Unfortunately, the behavioral phenotype of these mice, with a point mutation in the conserved tripeptide motif for coupling G proteins, was not reported, nor was any characterization of spontaneous spike generation.…”

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

“…S1A). Although the MOS is thought to detect volatile odorants and the VNS is thought to be important for the detection of nonvolatile pheromones, evidence shows that the MOS is also involved in pheromone detection (1)(2)(3)(4)(5)(6)(7)(8). Surgical blocking of odorant access to the MOE, but not surgical ablation of the vomeronasal epithelium (VNE), eliminates preference to odors from the opposite sex in ferrets (9,10).…”