Olfactory Receptor Patterning in a Higher Primate

Abstract

The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms.

Combinatorial effects of odorants on mouse behavior

“…Moreover, TMA-induced attraction required TAAR5 and PEA-induced aversion required TAAR4 (22,23). Together with the finding that individual fish and human TAARs recognize volatile amines aversive to those species (17,(24)(25)(26), these findings have suggested that the evolutionary conservation of the TAAR family may be linked to an ability to induce innate behaviors to volatile amines.…”

“…Like ORs, TAARs are evolutionarily conserved in vertebrates (15)(16)(17), suggesting that TAARs may have a distinct function. Moreover, sensory neurons expressing TAARs appear to comprise a separate lineage (18)(19)(20), and genes encoding ORs and TAARs have different nuclear locations (20), which may contribute to TAARs' segregated expression in different neurons.…”

“…At least some TAARs specifically recognize volatile amines, and two are required for behavioral attraction or avoidance to animal-derived amines (10,(21)(22)(23). In addition, one zebrafish TAAR ligand is aversive to fish (24), and one human TAAR detects an odorant aversive to humans as well as rotten fish (17,25,26). These observations have raised the possibility that the TAAR family may have an evolutionarily conserved ability to induce innate responses, particularly aversion.…”

Trace Amines and Their Receptors

“…Although TAARs are only distantly related to biogenic amine receptors and they also have no phylogenetic relationship with classic chemosensory receptors, it appears that all subfamilies of TAARs, with the exception of TAAR1, serve chemosensory functions in detecting socially or ecologically relevant olfactory cues (Liberles and Buck, 2006;Hussain et al, 2009;Horowitz et al, 2014;Liberles, 2015). Indeed, mammalian TAAR2-TAAR9 subfamilies, as well as teleost-specific TAARs, have distinct expression patterns in the olfactory system, being present in the olfactory epithelium, and neonatal Grueneberg ganglion but not in the vomeronasal organ (Liberles and Buck, 2006;Fleischer et al, 2007;Hussain et al, 2009).…”

Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

“…Ligands found thus far for TAARs are volatile amines, including several in mouse or predator urine (5,14,15). Ligands for a few mouse, fish, and human TAARs elicit aversive or attractive behaviors in their respective species, hinting at a conserved ability of TAARs to stimulate innate responses of potentially adaptive significance (5,6,14,16,17).…”