Concept: Olfactory system
Juxtaglomerular neurons represent one of the largest cellular populations in the mammalian olfactory bulb yet their role for signal processing remains unclear. We used two-photon imaging and electrophysiological recordings to clarify the properties of these cells and their functional organization in the juxtaglomerular space. Juxtaglomerular neurons coded for many perceptual characteristics of the olfactory stimulus such as (1) identity of the odorant, (2) odorant concentration, (3) odorant onset, and (4) offset. The odor-responsive neurons clustered within a narrow area surrounding the glomerulus with the same odorant specificity, with ~80% of responding cells located ≤20 μm from the glomerular border. This stereotypic spatial pattern of activated cells persisted at different odorant concentrations and was found for neurons both activated and inhibited by the odorant. Our data identify a principal glomerulus with a narrow shell of juxtaglomerular neurons as a basic odor coding unit in the glomerular layer and underline the important role of intraglomerular circuitry.
The aim of this study was to assess whether migration of thallium-201 (Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of Tl.
Most natural odors have sparse molecular composition. This makes the principles of compressed sensing potentially relevant to the structure of the olfactory code. Yet, the largely feedforward organization of the olfactory system precludes reconstruction using standard compressed sensing algorithms. To resolve this problem, recent theoretical work has shown that signal reconstruction could take place as a result of a low dimensional dynamical system converging to one of its attractor states. However, the dynamical aspects of optimization slowed down odor recognition and were also found to be susceptible to noise. Here we describe a feedforward model of the olfactory system that achieves both strong compression and fast reconstruction that is also robust to noise. A key feature of the proposed model is a specific relationship between how odors are represented at the glomeruli stage, which corresponds to a compression, and the connections from glomeruli to third-order neurons (neurons in the olfactory cortex of vertebrates or Kenyon cells in the mushroom body of insects), which in the model corresponds to reconstruction. We show that should this specific relationship hold true, the reconstruction will be both fast and robust to noise, and in particular to the false activation of glomeruli. The predicted connectivity rate from glomeruli to third-order neurons can be tested experimentally.
In the nasal olfactory epithelium, olfactory metabolic enzymes ensure odorant clearance from the olfactory receptor environment. This biotransformation of odorants into deactivated polar metabolites is critical to maintaining peripheral sensitivity and perception. Olfactory stimuli consist of complex mixtures of odorants, so binding interactions likely occur at the enzyme level and may impact odor processing. Here, we used the well-described model of mammary pheromone-induced sucking-related behavior in rabbit neonates. It allowed to demonstrate how the presence of different aldehydic odorants efficiently affects the olfactory metabolism of this pheromone (an aldehyde too: 2-methylbut-2-enal). Indeed, according to in vitro and ex vivo measures, this metabolic interaction enhances the pheromone availability in the epithelium. Furthermore, in vivo presentation of the mammary pheromone at subthreshold concentrations efficiently triggers behavioral responsiveness in neonates when the pheromone is in mixture with a metabolic challenger odorant. These findings reveal that the periphery of the olfactory system is the place of metabolic interaction between odorants that may lead, in the context of odor mixture processing, to pertinent signal detection and corresponding behavioral effect.
Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species' olfactory sensitivity. Analysis of odor structure-activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity.
Typically, ∼0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these “MouSensors.” In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 MouSensor. Moreover, a behavioral avoidance task demonstrates that specific odor detection thresholds are significantly decreased in multiple transgenic lines, expressing mouse or human ORs. We have developed a versatile platform to study gene choice and axon identity, to create biosensors with great translational potential, and to finally decode human olfaction.
Humans can discriminate several million different colors and almost half a million different tones, but the number of discriminable olfactory stimuli remains unknown. The lay and scientific literature typically claims that humans can discriminate 10,000 odors, but this number has never been empirically validated. We determined the resolution of the human sense of smell by testing the capacity of humans to discriminate odor mixtures with varying numbers of shared components. On the basis of the results of psychophysical testing, we calculated that humans can discriminate at least 1 trillion olfactory stimuli. This is far more than previous estimates of distinguishable olfactory stimuli. It demonstrates that the human olfactory system, with its hundreds of different olfactory receptors, far outperforms the other senses in the number of physically different stimuli it can discriminate.
Cancer cells and non-cancer cells differ in their metabolism and they emit distinct volatile compound profiles, allowing to recognise cancer cells by their scent. Insect odorant receptors are excellent chemosensors with high sensitivity and a broad receptive range unmatched by current gas sensors. We thus investigated the potential of utilising the fruit fly’s olfactory system to detect cancer cells. Using in vivo calcium imaging, we recorded an array of olfactory receptor neurons on the fruit fly’s antenna. We performed multidimensional analysis of antenna responses, finding that cell volatiles from different cell types lead to characteristic response vectors. The distances between these response vectors are conserved across flies and can be used to discriminate healthy mammary epithelial cells from different types of breast cancer cells. This may expand the repertoire of clinical diagnostics, and it is the first step towards electronic noses equipped with biological sensors, integrating artificial and biological olfaction.
One of the major challenges in olfaction research is to relate the structural features of the odorants to different features of olfactory system. However, no relationship has been yet discovered between the structure of the olfactory stimulus, and the structure of respiratory signal. This study reveals the plasticity of human respiratory signal in relation to ‘complex’ olfactory stimulus (odorant). We demonstrated that fractal temporal structure of respiration dynamics shifts towards the properties of the odorants used. The results show for the first time that more structurally complex a monomolecular odorant will result in less fractal respiratory signal. On the other hand, odorant with higher entropy will result the respiratory signal with lower entropy. The capability observed in this research can be further investigated and applied for treatment of patients with different respiratory diseases.
An important challenge in heart research is to make the relation between the features of external stimuli and heart activity. Olfactory stimulation is an important type of stimulation that affects the heart activity, which is mapped on Electrocardiogram (ECG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the ECG signal. This study investigates the relation between the structures of heart rate and the olfactory stimulus (odorant). We show that the complexity of the heart rate is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal heart rate. Also, odorant having higher entropy causes the heart rate having lower approximate entropy. The method discussed here can be applied and investigated in case of patients with heart diseases as the rehabilitation purpose.