Olfaction: Scents and sensibility

AbstractExpression of a receptor protein has, for the first time, been definitively correlated with sensitivity to a particular odorant. This receptor, expressed in the nematode Caenorhabditis elegans, appears to be distinct from the putative vertebrate odorant receptors

Nose thyself: individuality in the human olfactory genome

A link between a genetic polymorphism in an odorant receptor and variability in perception of the smell of the steroid androstenone

Regeneration of New Neurons is Preserved in Aged Vomeronasal Epithelia

During normal and diseased aging, it is thought the capacity for tissue regeneration and repair in neuronal tissues diminishes. In the peripheral olfactory system, stem cell reservoirs permit regeneration of olfactory and vomeronasal sensory neurons, a unique capacity among neurons. Following injury, a large number of new neurons can be regenerated in a young animal. However, it is unknown whether this capacity for renewal exists in aged proliferative populations. Here, we report that neuronal replacement-associated proliferation continues in the vomeronasal organ of aged (18-24 months) mice. In addition, the potential for the aged stem cell to yield a mature neuron persisted at the same rate as that observed in young animals. Furthermore, the robust regenerative capacity to respond to both acute and sustained injury following olfactory bulbectomy remains intact even in very old animals. Hence, the neuronal epithelium lining the vomeronasal organ is unique in that it contains stem cells capable of generating functional neurons throughout life and in the aged animal in particular. This persistent regenerative capacity provides hope for neuronal replacement therapies in the aged nervous system

A Painful Trp Can Be a Bonding Experience

The receptive field of the TRPA1 nociceptor is remarkably expansive when compared to other chemodetectors such as odorant receptors. The identification of a unique mechanism utilized by TRPA1 helps clarify how this protein can efficiently alert the cell to an array of reactive chemical agents, regardless of their structure

Action Potentials that Go the Distance

AbstractDendrodendritic inhibition between mitral and granule cells in the olfactory bulb is thought to play an important role in olfactory discrimination. In this issue of Neuron, Xiong and Chen (2002) explore the propagation of action potentials along the secondary dendrites of mitral cells and their modulation by dendrodendritic inhibition

High-Throughput Microarray Detection of Vomeronasal Receptor Gene Expression in Rodents

We performed comprehensive data mining to explore the vomeronasal receptor (V1R and V2R) repertoires in mouse and rat using the mm5 and rn3 genome, respectively. This bioinformatic analysis was followed by investigation of gene expression using a custom designed high-density oligonucleotide array containing all of these receptors and other selected genes of interest. This array enabled us to detect the specific expression of V1R and V2Rs which were previously identified solely based on computational prediction from gene sequence data, thereby establishing that these genes are indeed part of the vomeronasal system, especially the V2Rs. One hundred sixty-eight V1Rs and 98 V2Rs were detected to be highly enriched in mouse vomeronasal organ (VNO), and 108 V1Rs and 87 V2Rs in rat VNO. We monitored the expression profile of mouse VR genes in other non-VNO tissues with the result that some VR genes were re-designated as VR-like genes based on their non-olfactory expression pattern. Temporal expression profiles for mouse VR genes were characterized and their patterns were classified, revealing the developmental dynamics of these so-called pheromone receptors. We found numerous patterns of temporal expression which indicate possible behavior-related functions. The uneven composition of VR genes in certain patterns suggests a functional differentiation between the two types of VR genes. We found the coherence between VR genes and transcription factors in terms of their temporal expression patterns. In situ hybridization experiments were performed to evaluate the cell number change over time for selected receptor genes

Pharmacology of fragrance: odors and GPCRs

Odor receptors are the largest family of GPCR’s on the planet. The identification of this large family of genes by Buck and Axel in 1991 showed that they have much in common with the other 450 or so GPCRs found in the mammalian genome. From this one might imagine that they can be profitably studied by using techniques developed for standard GPCR pharmacology – ligand screening, structure activity relations, and a variety of modeling techniques. We have utilized synthetic chemistry to examine the structure-function activity of an odor receptor by utilizing a variety of synthetically designed ligands that demonstrate mechanisms for agonism, antagonism, partial agonism and reverse agonism. These analyses provide a theoretical picture of the requirements for a binding region within the receptor. The existence of a range of ligands – from antagonists to high affinity agonists - for a given receptor must be taken into account when considering the type of upstream brain circuits that might be required to reduce the complex diversity of odor stimuli to the simpler categories of fragrance perception. In addition to these common principles of pharmacology that can be applied profitably to odor receptors we suggest that the techniques and strategies of medicinal chemistry, normally targeted to a single specific receptor (e.g., dopamine, epinephrine, serotonin) can be modified for use in a large and varied receptor population. The med chem concept of bioisosterism, for example, may help to better define our thinking about broad and narrow tuning in receptors when applied to large numbers of receptors

Injury in Aged Animals Robustly Activates Quiescent Olfactory Neural Stem Cells

While the capacity of the olfactory epithelium (OE) to generate sensory neurons continues into middle age in mice, it is presumed that this regenerative potential is present throughout all developmental stages. However, little experimental evidence exists to support the idea that this regenerative capacity remains in late adulthood, and questions about the functionality of neurons born at these late stages remain unanswered. Here, we extend our previous work in the VNO to investigate basal rates of proliferation in the OE, as well as after olfactory bulbectomy, a commonly used surgical lesion. In addition, we show that the neural stem cell retains its capacity to generate mature olfactory sensory neurons in aged animals. Finally, we demonstrate that regardless of age, a stem cell in the OE, the horizontal basal cell (HBC), exhibits a morphological switch from a flattened, quiescent phenotype to a pyramidal, proliferative phenotype following chemical lesion in aged animals. These findings provide new insights into determining whether an HBC is active or quiescent based on a structural feature as opposed to a biochemical one. More importantly, it suggests that neural stem cells in aged mice are responsive to the same signals triggering proliferation as those observed in young mice

Axon fasciculation in the developing olfactory nerve

Olfactory sensory neuron (OSN) axons exit the olfactory epithelium (OE) and extend toward the olfactory bulb (OB) where they coalesce into glomeruli. Each OSN expresses only 1 of approximately 1,200 odor receptors (ORs). OSNs expressing the same OR are distributed in restricted zones of the OE. However, within a zone, the OSNs expressing a specific OR are not contiguous - distribution appears stochastic. Upon reaching the OB the OSN axons expressing the same OR reproducibly coalesce into two to three glomeruli. While ORs appear necessary for appropriate convergence of axons, a variety of adhesion associated molecules and activity-dependent mechanisms are also implicated. Recent data suggest pre-target OSN axon sorting may influence glomerular convergence. Here, using regional and OR-specific markers, we addressed the spatio-temporal properties associated with the onset of homotypic fasciculation in embryonic mice and assessed the degree to which subpopulations of axons remain segregated as they extend toward the nascent OB. We show that immediately upon crossing the basal lamina, axons uniformly turn sharply, usually at an approximately 90° angle toward the OB. Molecularly defined subpopulations of axons show evidence of spatial segregation within the nascent nerve by embryonic day 12, within 48 hours of the first OSN axons crossing the basal lamina, but at least 72 hours before synapse formation in the developing OB. Homotypic fasciculation of OSN axons expressing the same OR appears to be a hierarchical process. While regional segregation occurs in the mesenchyme, the final convergence of OR-specific subpopulations does not occur until the axons reach the inner nerve layer of the OB

Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray

Using a microarray, expression of 76% of predicted human olfactory receptor genes was detected in olfactory epithelia, and many were expressed in non-olfactory tissues