嗅觉受体基因的研究进展

嗅觉在动物的生命活动中起着重要的作用,与嗅觉相关的基因主要是嗅觉受体(Olfactory receptor,OR)基因。文章介绍了嗅觉受体基因的结构、表达调控、分布、分子进化及其多态性研究进展,并讨论了该基因与嗅觉功能和嗅觉障碍的关系。     

Effects of concentration and sniff flow rate on the rat electroolfactogram

Previous reports using the electroolfactogram (EOG) to study the spatial and temporal aspects of response in the rodent olfactory epithelium had focused on high odorant concentrations that gave large responses. This investigation has used lower concentrations to test the difference between responses in the rat dorsomedial and lateral recesses with a range of nasal flow rates and a range of chemical properties. The responses to a highly polar, more hydrophilic odorant changed more steeply with flow rate than responses to a very nonpolar, hydrophobic odorant. With low flow rates there was a response delay in the lateral recess, which is consistent with the models indicating lower flow rates in that region. We observed significant volume conduction effects in which large responses in the dorsomedial region obscured smaller initial portions of the lateral responses. These effects could be removed by destroying the dorsomedial response with a high concentration of a low molecular weight ester. We caution that investigators of EOG recordings from the intact epithelium must attend to the possible presence of volume conduction, which can be assessed by attention to the selectivity of odorant response, response waveform, and response latency.     

Inflammatory obstruction of the olfactory clefts and olfactory loss in humans: a new syndrome?

The first step in the olfactory perception is the activation by odorants of sensory neurones in the olfactory epithelium. In humans, this sensory epithelium is located at 2 narrow passages, the olfactory clefts, at the upper part of the nasal cavities. Little is known about the physiology of these clefts. We examined, in 34 patients, the impact of obstructed clefts upon detection and postlearning identification of 5 odorants. The location and extension of the obstructions were assessed using endoscopy, CT scans, and MRI. The inflammatory obstruction was usually bilateral, extending anteroposteriorly, and confined to the clefts, with no sign of obstruction or any inflammatory disease in the rest of the nasal cavities and sinuses. When tested with 5 odorants, these patients showed greatly impaired olfaction compared with a group of 73 normosmic subjects. The majority of these 34 patients had sensory deficits equivalent to that found in another group of 41 congenital anosmic patients, where inspection with MRI indicated the lack of olfactory bulbs. This study demonstrates that the olfactory clefts, in human, function as an entity that is different from other regions of the nasal cavity and is the target for local inflammatory events that are apparently not responding to corticoid and antibiotic treatments.     

磁共振脑功能成像在小动物嗅觉研究中的应用

综述了磁共振脑功能成像(functional MRI,fMRI)在嗅觉研究中的应用,着重介绍fMRI在小动物嗅觉研究中的优势,以及近10年来fMRI在嗅球(olfactory bulb,OB)信息编码、处理和传输机制研究中所取得的进展．作为人类最古老的感觉方式之一,整个嗅觉系统(除鼻腔中的嗅细胞)都属于边缘系统,这赋予嗅觉系统一般的感觉功能和许多不为人所熟知的对情感、记忆以及生理和心理状态调控的功能．同时,由于缺乏有效手段,其内在性也使得嗅觉系统在大脑中的信息编码、处理、传输和感知等机制的研究极为困难．fMRI由于具有相对高的时间和空间分辨率,并可以无创地、重复地观测大脑任何部位的神经活动而被广泛应用于神经科学的研究．fMRI在嗅觉系统的应用使我们对人的嗅觉高级中枢感知机制方面的研究取得了一定的进展,而嗅球为嗅觉信息编码和处理中心,由于其尺寸和人体MRI空间分辨率的限制,对人OB中编码机制的研究一直无法进行．     

Adult Neurogenesis in the Olfactory System: Improving Performance for Difficult Discrimination Tasks?

What is the function of new neurons entering the olfactory bulb? Many insights regarding the molecular control of adult neurogenesis have been uncovered, but the purpose of new neurons entering the olfactory bulb has been difficult to ascertain. Here, studies investigating the role of adult neurogenesis in olfactory discrimination in mice are reviewed. Studies in which adult neurogenesis is affected are highlighted, with a focus on the role of environment enrichment and what happens during ageing. There is evidence for a role of adult neurogenesis in fine discrimination tasks, as underscored by studies that enhance adult neurogenesis. This is also observed in ageing studies, where older mice with reduced levels of adult neurogenesis perform poorly in olfactory discrimination. Differences in methodology that could account for alternative conclusions, and the importance of specificity in methods being used to investigate the effect of adult neurogenesis in olfactory performance are emphasized.     

Differential development of odorant receptor expression patterns in the olfactory epithelium: a quantitative analysis in the mouse septal organ

The rodent olfactory epithelium expresses more than 1000 odorant receptors (ORs) with distinct patterns, yet it is unclear how such patterns are established during development. In the current study, we investigated development of the expression patterns of different ORs in the septal organ, a small patch of olfactory epithelium predominantly expressing nine identified ORs. The presumptive septal organ first appears at about embryonic day 16 (E16) and it completely separates from the main olfactory epithelium (MOE) at about postnatal day 7 (P7). Using in situ hybridization, we quantified the densities of the septal organ neurons labeled by specific RNA probes of the nine abundant OR genes from E16 to postnatal 3 months. The results indicate that olfactory sensory neurons (OSNs) expressing different ORs have asynchronous temporal onsets. For instance, MOR256-17 and MOR236-1 cells are present in the septal organ at E16; however, MOR0-2 cells do not appear until P0. In addition, OSNs expressing different ORs show distinct developmental courses and reach their maximum densities at different stages ranging from E16 (e.g. MOR256-17) to 1 month (e.g. MOR256-3 and MOR235-1). Furthermore, early onset does not correlate with high abundance in adult. This study reveals a dynamic composition of the OSNs expressing different ORs in the developing olfactory epithelium.     

Anatomical contributions to odorant sampling and representation in rodents: zoning in on sniffing behavior

Odorant sampling behaviors such as sniffing bring odorant molecules into contact with olfactory receptor neurons (ORNs) to initiate the sensory mechanisms of olfaction. In rodents, inspiratory airflow through the nose is structured and laminar; consequently, the spatial distribution of adsorbed odorant molecules during inspiration is predictable. Physicochemical properties such as water solubility and volatility, collectively called sorptiveness, interact with behaviorally regulable variables such as inspiratory flow rate to determine the pattern of odorant deposition along the inspiratory path. Populations of ORNs expressing the same odorant receptor are distributed in strictly delimited regions along this inspiratory path, enabling different deposition patterns of the same odorant to evoke different patterns of neuronal activation across the olfactory epithelium and in the olfactory bulb. We propose that both odorant sorptive properties and the regulation of sniffing behavior may contribute to rodents' olfactory capacities by this mechanism. In particular, we suggest that the motor regulation of sniffing behavior is substantially utilized for purposes of "zonation" or the direction of odorant molecules to defined intranasal regions and hence toward distinct populations of receptor neurons, pursuant to animals' sensory goals.     

Topographical relation between the olfactory bulb and the olfactory tract in tench (Tinca tinca L)

Electrical activity was recorded from single cells in the olfactorybulb when electrically stimulating the medial and lateral olfactorytract and when stimulating the olfactory epithelium with aminoacids. Bulbar units excited by stimulation of the medial olfactorytract were found in the medial and middle parts of the bulb.Neurones in the dorso-lateral part of the bulb were excitedby stimulation of lateral tract. Units inhibited by stimulationof the lateral or medial olfactory tracts had a reversed distributionwith the majority found in the medial or lateral parts of thebulb respectively. The chemicals tested induced changes in thedischarge of units mainly situated in the lateral part of thebulb.     

Mosaic activity patterns and their relation to perceptual similarity: open discussions on the molecular basis and circuitry of odor recognition

Enormous advances have been made in the recent years in regard to the mechanisms and neural circuits by which odors are sensed and perceived. Part of this understanding has been gained from parallel studies in insects and rodents that show striking similarity in the mechanisms they use to sense, encode, and perceive odors. In this review, we provide a short introduction to the functioning of olfactory systems from transduction of odorant stimuli into electrical signals in sensory neurons to the anatomical and functional organization of the networks involved in neural representation of odors in the central nervous system. We make emphasis on the functional and anatomical architecture of the first synaptic relay of the olfactory circuit, the olfactory bulb in vertebrates and the antennal lobe in insects. We discuss how the exquisite and conserved architecture of this structure is established and how different odors are encoded in mosaic activity patterns. Finally, we discuss the validity of methods used to compare activation patterns in relation to perceptual similarity.

     

Stimulation of olfactory receptors alters regulation of [Cai] in olfactory neurons of the catfish (Ictalurus punctatus)

Summary Intracellular calcium was measured in single olfactory neurons from the channel catfish (Icatalurus punctatus) using the fluorescent Ca²⁺ indicator fura 2. In 5% of the cells, olfactory stimuli (amino acids) elicited an influx of calcium through the plasma membrane which led to a rapid transient increase in intracellular calcium concentration. Amino acids did not induce release of calcium from internal stores in these cells. Some cells responded specifically to one stimulus (l-alanine,l-arginine,l-norleucine andl-glutamate) while one cell responded to all stimuli. An increase in intracellular calcium could also be elicited in 50% of the cells by direct G-protein stimulation using aluminum fluoride. Because the fraction of cells which respond to direct G-protein stimulation is substantially larger than the fraction of cells responding to amino acids, we tested for possible damage of receptor proteins due to exposure of the olfactory neurons to papain during cell isolation. We find that pretreatment with papain does not alter specific binding ofl-alanine andl-arginine to olfactory receptor sites in isolated olfactory cilia. The results are discussed in terms of their relevance to olfactory transduction.