An Olfactory Subsystem that Mediates High-Sensitivity Detection of Volatile Amines

Abstract

SUMMARY Olfactory stimuli are detected by over 1,000 odorant receptor genes in mice, with each receptor being mapped to specific glomeruli in the olfactory bulb. The Trace Amine-Associated Receptors (TAARs) are a small family of evolutionarily conserved olfactory receptors whose contribution to olfaction remains enigmatic. Here, we show that a majority of the TAARs are mapped to a discrete subset of glomeruli in the dorsal olfactory bulb of the mouse. This TAAR projection is distinct from the previously described class I and class II domains, and is formed by a sensory neuron population that is restricted to express TAAR genes prior to choice. We further show that the dorsal TAAR glomeruli are selectively activated by low concentrations of amines. Our data uncover a hard-wired, parallel input stream in the main olfactory pathway that is specialized for the detection of volatile amines.

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

“…Some are expressed in only the dorsal or ventral OE and others in both domains. In knockout (KO) mice with a single Taar gene replaced by a reporter gene, 50-60% of OSNs expressing the reporter also expressed a functional Taar gene (21,22). Mutation of one dorsal Taar (Taar4) led to the secondary expression of mostly dorsal Taars (21), suggesting that there might be subsets of TAAR OSNs that differ in the Taar genes they can express.…”

“…OR-expressing OSNs are thought to randomly select one odorant receptor (Olfr) allele for expression, but choose a second Olfr allele to express if the first one fails to produce a functional protein (18)(19)(20). A high proportion of OSNs that express a mutated Taar gene also express a functional Taar allele, suggesting similar mechanisms for Olfr and Taar "gene choice," but one tailored to Taars (21,22).…”

“…Whereas Olfr genes are found in clusters at multiple loci on most chromosomes (11), Taar genes are clustered at a single chromosomal locus (23). Like Olfr genes, different Taar genes can be expressed in different spatial domains within the OE (13,21). The differential expression suggests the existence of additional gene regulatory mechanisms that act at the level of the Taar gene locus, but remain to be elucidated.…”

High-affinity olfactory receptor for the death-associated odor cadaverine

“…27). In vitro studies did not identify a high-affinity cadaverine receptor among mouse, rat, or human TAARs (18), although cadaverine reportedly activates TAAR-containing glomeruli in mice at high concentrations (8). Other mammalian TAARs also detect aversive amines; for example, isoamylamine (TAAR3) and 2-phenylethylamine (TAAR4), both likewise produced by decarboxylation of amino acids (16,18,19,32).…”

“…Cadaverine and putrescine evoke electrophysiological responses in the olfactory epithelium of two fish species (2, 6) and cadaverine-responsive olfactory sensory neurons and glomeruli have been identified in the mouse (7,8). However, chemosensory receptors that detect cadaverine or related diamines are unknown in any species, and could provide valuable tools to study how the olfactory system mediates innate aversion or attraction.…”