PubMed Health⌕ Search

Biomedical subjects

Linda B Buck

Publications and source records attributed to Linda B Buck.

10 recordsLinked to original sources

A second class of chemosensory receptors in the olfactory epithelium.

The mammalian olfactory system detects chemicals sensed as odours as well as social cues that stimulate innate responses. Odorants are detected in the nasal olfactory epithelium by the odorant receptor family, whose approximately 1,000 members allow the discrimination of a myriad of odorants. Here we report the discovery of a second family of receptors in the mouse olfactory epithelium. Genes encoding these receptors, called 'trace amine-associated receptors' (TAARs), are present in human, mouse and fish. Like odorant receptors, individual mouse TAARs are expressed in unique subsets of neurons dispersed in the epithelium. Notably, at least three mouse TAARs recognize volatile amines found in urine: one detects a compound linked to stress, whereas the other two detect compounds enriched in male versus female urine-one of which is reportedly a pheromone. The evolutionary conservation of the TAAR family suggests a chemosensory function distinct from odorant receptors. Ligands identified for TAARs thus far suggest a function associated with the detection of social cues.

Amines↗

RETRACTED: Combinatorial effects of odorant mixes in olfactory cortex.

In mammals, each odorant is detected by a combination of different odorant receptors. Signals from different types of receptors are segregated in the nose and the olfactory bulb, but appear to be combined in individual neurons in the olfactory cortex. Here, we report that binary odorant mixes stimulate cortical neurons that are not stimulated by their individual component odorants. We propose that cortical neurons require combinations of receptor inputs for activation and that merging the receptor codes of two odorants provides novel combinations of receptor inputs that stimulate neurons beyond those activated by the single odorants. These findings may explain why odorant mixtures can elicit novel odor percepts in humans.

Animals↗

Feedback loops link odor and pheromone signaling with reproduction.

Pheromones can have profound effects on reproductive physiology and behavior in mammals. To investigate the neural circuits underlying these effects, we used a genetic transneuronal tracer to identify neurons that synapse with GnRH (LHRH) neurons, the key regulators of reproduction. We then asked whether the connected neurons are presynaptic or postsynaptic to GnRH neurons and analyzed their responses to chemosensory cues. Surprisingly, these experiments indicate that GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Moreover, feedback loops are evident whereby GnRH neurons could influence both odor and pheromone processing. Remarkably, approximately 800 GnRH neurons communicate with approximately 50,000 neurons in 53 functionally diverse brain areas, with some connections exhibiting sexual dimorphism. These studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.

Amygdala↗

Odor maps in the olfactory cortex.

In the olfactory system, environmental chemicals are deconstructed into neural signals and then reconstructed to form odor perceptions. Much has been learned about odor coding in the olfactory epithelium and bulb, but little is known about how odors are subsequently encoded in the cortex to yield diverse perceptions. Here, we report that the representation of odors by fixed glomeruli in the olfactory bulb is transformed in the cortex into highly distributed and multiplexed odor maps. In the mouse olfactory cortex, individual odorants are represented by subsets of sparsely distributed neurons. Different odorants elicit distinct, but partially overlapping, patterns that are strikingly similar among individuals. With increases in odorant concentration, the representations expand spatially and include additional cortical neurons. Structurally related odorants have highly related representations, suggesting an underlying logic to the mapping of odor identities in the cortex.

Animals↗

The human olfactory receptor gene family.

Humans perceive an immense variety of chemicals as having distinct odors. Odor perception initiates in the nose, where odorants are detected by a large family of olfactory receptors (ORs). ORs have diverse protein sequences but can be assigned to subfamilies on the basis of sequence relationships. Members of the same subfamily have related sequences and are likely to recognize structurally related odorants. To gain insight into the mechanisms underlying odor perception, we analyzed the human OR gene family. By searching the human genome database, we identified 339 intact OR genes and 297 OR pseudogenes. Determination of their genomic locations showed that OR genes are unevenly distributed among 51 different loci on 21 human chromosomes. Sequence comparisons showed that the human OR family is composed of 172 subfamilies. Types of odorant structures that may be recognized by some subfamilies were predicted by identifying subfamilies that contain ORs with known odor ligands or human homologs of such ORs. Analysis of the chromosomal locations of members of each OR subfamily revealed that most subfamilies are encoded by a single chromosomal locus. Moreover, many loci encode only one or a few subfamilies, suggesting that different parts of the genome may, to some extent, be involved in the detection of different types of odorant structural motifs.

Animals↗

The mouse olfactory receptor gene family.

In mammals, odor detection in the nose is mediated by a diverse family of olfactory receptors (ORs), which are used combinatorially to detect different odorants and encode their identities. The OR family can be divided into subfamilies whose members are highly related and are likely to recognize structurally related odorants. To gain further insight into the mechanisms underlying odor detection, we analyzed the mouse OR gene family. Exhaustive searches of a mouse genome database identified 913 intact OR genes and 296 OR pseudogenes. These genes were localized to 51 different loci on 17 chromosomes. Sequence comparisons showed that the mouse OR family contains 241 subfamilies. Subfamily sizes vary extensively, suggesting that some classes of odorants may be more easily detected or discriminated than others. Determination of subfamilies that contain ORs with identified ligands allowed tentative functional predictions for 19 subfamilies. Analysis of the chromosomal locations of members of each subfamily showed that many OR gene loci encode only one or a few subfamilies. Furthermore, most subfamilies are encoded by a single locus, suggesting that different loci may encode receptors for different types of odorant structural features. Comparison of human and mouse OR subfamilies showed that the two species have many, but not all, subfamilies in common. However, mouse subfamilies are usually larger than their human counterparts. This finding suggests that humans and mice recognize many of the same odorant structural motifs, but mice may be superior in odor sensitivity and discrimination.

Animals↗

Olfactory receptors and odor coding in mammals.

Humans and other mammals perceive a vast number of volatile chemicals as having distinct odors. This ability derives from the existence of a large family of olfactory receptors that number about 350 in man and 1000 in mice. Individual odorants activate distinct combinations of olfactory receptors, generating an immense array of combinatorial receptor codes that define odorant identities. Sensory neurons in the nose express only one receptor type each and connect to the olfactory bulb in a spatially organized manner that yields a stereotyped sensory map. A secondary projection from the bulb to the cortex transforms receptor inputs, generating another, different stereotyped map that may permit the integration of inputs from combinations of receptors. Another olfactory structure in the nasal septum of animals, the vomeronasal organ, has two additional receptor families that detect pheromones and induce hormonal and behavioral responses through a different projection to the brain.

Animals↗

Olfactory axon pathfinding: who is the pied piper?

Mammalian olfactory sensory neurons that express a particular odorant receptor (OR) project axons to the same few glomeruli in the olfactory bulb. In this issue of Neuron, Vassalli et al. use OR minigenes that coexpress histochemical markers and show that the determinants in the sensory neurons required to generate the stereotyped olfactory bulb map are the same as those needed for appropriate expression of the OR.

Animals↗