Olfactory training in specific anosmia to androstenone and its association with genetic variations of OR7D4.

Short-term, repeated exposure to odors, "olfactory training" (OT), improves olfactory function. Clinically, this works not only for trauma- or disease-related olfactory impairment but also in people with specific anosmia. Androstenone is an odorant for which the frequent occurrence of specific anosmia is already known.

Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches.

Zebra finches are sexually dimorphic vocal learners. Males learn to sing by imitating mature conspecifics, but females do not. Absence of song in females is associated with partial atrophy and apparent repression of several vocal learning brain regions during development.

An odorant receptor for a key odor constituent of ambergris.

Ambergris, a substance derived from the digestive system of sperm whales, has been valued for centuries for its unique aromatic properties. However, historical accounts indicate that certain human populations, particularly in East Asia, utilized ambergris without regard for its odor quality. These observations suggest that ambergris offers a model for studying how pleasant olfactory perception and its regional variations are constructed.

Antagonists Enhance Cell-Surface Expression of Mammalian Odorant Receptors.

Functional characterization of vertebrate odorant receptors (ORs), members of the G protein-coupled receptor (GPCR) family, is essential for understanding olfaction. However, the functional expression of ORs in heterologous cells is often challenging, at least partly caused by structural instability in non-olfactory cells. Antagonists have been shown to restore membrane expression of some non-olfactory GPCR mutants, likely by transient increase in structural stability upon antagonist binding.

Engineered odorant receptors illuminate the basis of odour discrimination.

How the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations remains poorly understood. Vertebrate animals perceive odours through G protein-coupled odorant receptors (ORs). In humans, around 400 ORs enable the sense of smell.

Finding the sweet spot of the insect gustatory receptor.

In a recent issue of Nature, Gomes et al. utilized structural, experimental, and computational biology to investigate the ligand-gated activation of BmGr9, an insect gustatory receptor specifically tuned to D-fructose. Together with two other studies published elsewhere, they are the first to describe how sugars bind to insect gustatory receptors.

Role of iRhom2 in Olfaction: Implications for Odorant Receptor Regulation and Activity-Dependent Adaptation.

The cell surface metalloprotease ADAM17 (a disintegrin and metalloprotease 17) and its binding partners iRhom2 and iRhom1 (inactive Rhomboid-like proteins 1 and 2) modulate cell-cell interactions by mediating the release of membrane proteins such as TNFα (Tumor necrosis factor α) and EGFR (Epidermal growth factor receptor) ligands from the cell surface. Most cell types express both iRhoms, though myeloid cells exclusively express iRhom2, and iRhom1 is the main iRhom in the mouse brain. Here, we report that iRhom2 is uniquely expressed in olfactory sensory neurons (OSNs), highly specialized cells expressing one olfactory receptor (OR) from a repertoire of more than a thousand OR genes in mice.

A chemical signal in human female tears lowers aggression in males.

Rodent tears contain social chemosignals with diverse effects, including blocking male aggression. Human tears also contain a chemosignal that lowers male testosterone, but its behavioral significance was unclear. Because reduced testosterone is associated with reduced aggression, we tested the hypothesis that human tears act like rodent tears to block male aggression.

Engineered odorant receptors illuminate structural principles of odor discrimination.

A central challenge in olfaction is understanding how the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations. Vertebrate animals perceive odors via G protein-coupled odorant receptors (ORs). In humans, ~400 ORs enable the sense of smell.

Target-Captured mRNA from Murine Olfactory Bulb.

The external world is perceived via sensory receptors arranged in highly organized systems according to functional strategies, which in turn reflect features of critical importance to both the sense and the animal. Thus describing the receptor organization and functional strategies of olfaction, the sense of smell, is crucial for a concrete understanding of the fundamental principles of the system's architecture. Sensory processing in olfactory systems is organized across olfactory bulb (OB) glomeruli, wherein axons of peripheral sensory neurons expressing the same olfactory receptor (OR) co-terminate to transmit receptor-specific activity to mitral/tufted cells, projection neurons in the olfactory bulb.

Measuring Cell Surface Expression of Odorant Receptors via Flow Cytometry.

Odorant receptor proteins (ORs) have highly variable cell surface expression levels. The majority of both human and murine ORs depend on chaperone proteins to traffic from the endoplasmic reticulum to the cell surface, while a limited subset of ORs express at high levels independently. Quantifying these heterogeneous expression levels is of high import for understanding the trafficking and stability of these integral-transmembrane proteins and for normalizing in vitro activation assays.

Activity-Dependent Labeling of Olfactory Sensory Neurons Using RNA Fluorescence In Situ Hybridization Followed by Phospho-S6 Immunofluorescence.

This microscope-based method allows demonstrating that an odorant receptor responded to an odorant in vivo. In sections of olfactory epithelium from odorant-exposed mice, the subpopulation of olfactory sensory neurons expressing a particular odorant receptor type is labeled using RNA fluorescence in situ hybridization. Sequential immunofluorescence against the phosphorylated S6 ribosomal subunit reveals the activated olfactory sensory neurons.

Antagonistic interactions between odorants alter human odor perception.

The olfactory system uses hundreds of odorant receptors (ORs), the largest group of the G-protein-coupled receptor (GPCR) superfamily, to detect a vast array of odorants. Each OR is activated by specific odorous ligands, and like other GPCRs, antagonism can block activation of ORs. Recent studies suggest that odorant antagonisms in mixtures influence olfactory neuron activities, but it is unclear how this affects perception of odor mixtures.

Identification and Characterization of Proteins That Are Involved in RTP1S-Dependent Transport of Olfactory Receptors.

Olfaction is mediated via olfactory receptors (ORs) that are expressed on the cilia membrane of olfactory sensory neurons in the olfactory epithelium. The functional expression of most ORs requires the assistance of receptor-transporting proteins (RTPs). We examined the interactome of RTP1S and OR via proximity biotinylation.

Structural basis of odorant recognition by a human odorant receptor.

Our sense of smell enables us to navigate a vast space of chemically diverse odour molecules. This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome. How odorants are recognized by odorant receptors remains unclear.

Genetic and functional odorant receptor variation in the Homo lineage.

Humans, Neanderthals, and Denisovans independently adapted to a wide range of geographic environments and their associated food odors. Using ancient DNA sequences, we explored the function of thirty odorant receptor genes in the genus . Our extinct relatives had highly conserved olfactory receptor sequence, but humans did not.

Sex steroid hormone synthesis, metabolism, and the effects on the mammalian olfactory system.

Sex steroid hormones influence olfactory-mediated social behaviors, and it is generally hypothesized that these effects result from circulating hormones and/or neurosteroids synthesized in the brain. However, it is unclear whether sex steroid hormones are synthesized in the olfactory epithelium or the olfactory bulb, and if they can modulate the activity of the olfactory sensory neurons. Here, we review important discoveries related to the metabolism of sex steroids in the mouse olfactory epithelium and olfactory bulb, along with potential areas of future research.

An odorant receptor that senses four classes of musk compounds.

Musk was originally identified in male musk deer and other mammals to mark territories and attract females. In humans, musk compounds are widely used in perfumes and consumer products for their superior perceptual odor quality. Strikingly diverse natural and synthetic chemicals have exhibited a similar "musky" odor, which has resulted in diverse models of musk odor perception and raises questions regarding the simplistic associations between chemical features and odor quality.

Olfactory receptors in macrophages and inflammation.

Olfactory receptors (ORs) that bind odorous ligands are the largest family of G-protein-coupled receptors. In the olfactory epithelium, approximately 400 and 1,100 members are expressed in humans and mice, respectively. Growing evidence suggests the extranasal functions of ORs.

Decoding the olfactory map through targeted transcriptomics links murine olfactory receptors to glomeruli.

Sensory processing in olfactory systems is organized across olfactory bulb glomeruli, wherein axons of peripheral sensory neurons expressing the same olfactory receptor co-terminate to transmit receptor-specific activity to central neurons. Understanding how receptors map to glomeruli is therefore critical to understanding olfaction. High-throughput spatial transcriptomics is a rapidly advancing field, but low-abundance olfactory receptor expression within glomeruli has previously precluded high-throughput mapping of receptors to glomeruli in the mouse.

Interactions among key residues regulate mammalian odorant receptor trafficking.

Odorant receptors (ORs) expressed in mammalian olfactory sensory neurons are essential for the sense of smell. However, structure-function studies of many ORs are hampered by unsuccessful heterologous expression. To understand and eventually overcome this bottleneck, we performed heterologous expression and functional assays of over 80 OR variants and chimeras.

Large-Scale G Protein-Coupled Olfactory Receptor-Ligand Pairing.

G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diverse. This work investigated how the amino-acid sequences of olfactory receptors (ORs)-the largest GPCR family-encode diversified responses to various ligands. We established a proteochemometric (PCM) model based on OR sequence similarities and ligand physicochemical features to predict OR responses to odorants using supervised machine learning.