A Gas chromatographic (GLPC) model for the sense of smell. Variation of olfactory sensitivity with conditions of stimulation☆
Abstract
Computer simulation of an olfactory detector has been developed using a chemical kinetic scheme originally proposed by McNab and Koshland for bacterial chemotaxis. This model describes response as a function of two opposed reactions, both of which are activated by odorant. One reaction turns on response, while its opponent shuts it off. Net response to various stimulus profiles is compared to psychophysical experiments, with particular attention paid to simulating magnitude estimation and odor adaptation results. Effects of the access route to this detector are evaluated. Transport of odorant molecules is treated as having two sequential steps: step (i), airborne odorant is carried parallel to a retentive layer (mucus) into the detector region; step (ii), molecules diffuse through the retentive layer to the detector. Step (i) is represented as analogous to GLPC on an open tubular column. Each step has a characteristic time constant, which is proportional to (distance)2/diffusion coefficient. Response to highly volatile odorants tends to be limited by step (ii), while odorants of low volatility approach the step (i) limit. Sensitivity at both limits is attenuated by increasing the thickness of the retentive layer, but sensitivity at the step (i) limit is also affected by changes in air passageway and airflow characteristics. This picture can be used to explain variations in women's sensitivity to odorants of low volatility with the menstrual cycle, while their detection of volatile odorants fluctuates to a much lesser extent.
References (34)
- T.V. Getchell et al.
Biophys. J
(1980) - D.E. Hornung et al.
Brain Res
(1977) - H. Hoshikawa et al.
J. theor. Biol
(1978) - N. Kamo et al.
J. theor. Biol
(1980) - J. Amoore
Chem. Senses Flavour
(1977) - B. Berglund et al.
Percept. Psychophys
(1971) - B. Berglund et al.
Sens. Processes
(1978) - H. Bostock
- W.S. Cain
Sens. Processes
(1976) - W.S. Cain et al.
JAMA
Percept. Psychophys
Commun. ACM
J. Physiol
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A numerical model of nasal odorant transport for the analysis of human olfaction
1997, Journal of Theoretical BiologyThe transport and uptake of inspired odorant molecules in the human nasal cavity were determined using an anatomically correct three-dimensional finite element model. The steady-state equations of motion and continuity were first solved to determine laminar flow patterns of odorous air at quiet breathing flow rates. The air stream entering the ventral tip of the naris travelled to the olfactory slit, and then passed through the slit in nearly a straight path without forming separated recirculating zones. The fraction of volumetric flow passing through the olfactory airway was about 10%, and remained nearly constant with variations in flow rate. The three-dimensional inspiratory velocity field was used in the solution of the uncoupled steady convective-diffusion equation to determine the concentration field in the airways and odorant mass flux at the nasal walls. The mass-transfer boundary condition used at the nasal cavity wall included the effects of solubility and diffusivity of odorants in the mucosal lining, and the thickness of the mucus layer. The total olfactory flux of odorants, that is highly correlated with perceived odor intensity, was determined as a function of all transport parameters in our model. Increase in nasal flow rate at a constant inlet concentration resulted in an increase in total olfactory uptake for all odorants. However, with increase in flow rate, the fractional uptake, i.e., total olfactory flux normalized by convective flux at the inlet, decreased for poorly soluble odorants, while it increased for highly soluble odorants. The pattern of flux (or imposed patterning) across the olfactory mucosa, that carries information concerning odor identity, was also determined as a function of transport parameters. There was an overall decrease in odorant flux as the location on the olfactory surface was varied from the anterior towards the posterior and from the inferior towards the superior ends. The flux pattern became more uniform, i.e., the steepness of the flux gradients across the olfactory surface decreased, as the mucus solubility of the odorants decreased. Different odorants generated discernibly different flux patterns across the olfactory mucosa that may contribute to the encoding of odor quality. Variation of total olfactory flux with time after cessation of airflow was determined by solving the unsteady diffusion equation in the air-phase. The flux decreased approximately exponentially with time. The rate of decay decreased as solubility and diffusivity decreased, but was very rapid over a wide range of the parameters, with time constants of less that 0.5 s for most odorants, implying a rapid decrease in perceived odor intensity with cessation of nasal airflow.
A mass transport model of olfaction
1994, Journal of Theoretical BiologyA theoretical model of olfaction involving all the major mechanisms in the mass transport of odorant molecules from inspired air to the olfactory receptors is developed. The mechanisms included are: (i) convective bulk flow of odorant molecules to the olfactory region of the nasal cavity by inhaled air, (ii) lateral transport of odorant molecules from the flowing gas stream in the olfactory region onto the olfactory mucus surface, (iii) sorption of odorant molecules into the mucus at the air-mucus interface, (iv) diffusion of odorant molecules through the mucus layer, and (v) interaction of odorant molecules with the olfactory receptor cells. The model is solved to yield the olfactory response as a function of various physical variables such as the inspiratory flow rate, the mass transfer coefficient, the initial concentration of odorant molecules in the inhaled air, the length of the olfactory mucosa, the thickness of the olfactory mucosa, and the air-mucus partitioning (or solubility in the mucus) of odorant molecules. It was determined that the flow rate of the odorant carrier gas, length of the olfactory mucus surface, and the solubility of odorant molecules in the olfactory mucus should play important roles in determining the odor intensity for these odorants. The model predicts that, given adequate mucus surface for sorption, increase in the flow rate results in an increase in perceived odor intensity for the readily sorbed or highly soluble odorants (such as carvone) and a decrease in odor intensity for the poorly sorbed or insoluble odorants (such as octane). With a substantial decrease in the mucus surface for sorption, increase in the flow rate results in a decrease in perceived odor intensity for all odorants. The theoretical results show good agreement with various experimental data obtained from both psychophysical and electrophysiological studies of olfaction using animals and human subjects.
Small odorant molecules affect steady state properties of monolayers
1989, Thin Solid FilmsInteractions of organic compounds with polar lipid monolayers have been widely studied and fall into two general categories: polar molecules (often electrically charged), which interact primarily with head groups, and non-polar molecules, which interact with tail groups. This study presents results for a typical odorant molecule, cyclohexanone, which is semipolar in the sense that the dipolar functional group (a carbonyl) is part of a small, non-polar hydrocarbon ring. Thermodynamic measurements on monolayers prepared from pure L-α- dipalmitoyllecithin (DPPC) reveal effects from cyclohexanone in the subphase on the ΔG for compression, which exhibits a maximum as a function of temperature, suggesting that interaction of the cyclohexane ring with hydrophobic tail groups dominates below 297 K, while interaction of the carbonyl function with head groups dominates above 297 K. Measurements of the surface dipole moment confirm this inference: when cyclohexanone is in the subphase the surface dipole moment is less than the value of μ for pure DPPC when the temperature is below 297 K. Above 297 K the surface dipole moment in the presence of cyclohexanone has a value greater than or equal to μ for pure DPPC. Variations in orientation of small molecules within lipid assemblies might conceivably contribute to membrane recognition of an odorant.
Male hamster copulatory responses to a high molecular weight fraction of vaginal discharge: Effects of vomeronasal organ removal
1984, Physiology and BehaviorThe importance of the vomeronasal (accessory olfactory) system for the copulatory responses of male hamsters to a high molecular weight fraction (HMF) of vaginal discharge was assessed in animals that had their vomeronasal organs (VNO) removed. These organs were extirpated bilaterally using an oral approach through the palate so as to eliminate the peripheral afferents to the accessory olfactory bulb (AOB) with minimal or no damage to the main olfactory system. The selective peripheral deafferentation procedure was verified by applying horseradish peroxidase intranasally following intraperitoneal injections of epinephrine to facilitate the vomeronasal pumping mechanism that draws fluids into the VNO. Heavy, bilateral anterograde labeling was evident in the olfactory nerve afferents within the main olfactory bulb of males that had their VNO removed and of animals that received sham surgery. Sham-operated males also had heavy, bilateral labeling in the vomeronasal nerve afferents within the AOB, whereas no such labeling occurred among animals with bilateral removal of the VNO. In sham-operated animals, both the HMF and the unfractionated discharge significantly increased the incidence of intromission attempts toward anesthetized males (surrogate females) whose hindquarters were scented with these stimuli. The unfractionated discharge also produced a significant elevation of overt copulatory behavior in males with selective peripheral deafferentation of the vomeronasal system, whereas the HMF did not facilitate copulatory behavior in these animals. These results are consistent with the hypotheses (1) that the vomeronasal system is specialized for the reception of relatively nonvolatile constituents of excretions or secretions that are used in pheromonal communication, (2) that gustatory processing cannot account for the aphrodisiac activity in the HMF, and (3) that both the vomeronasal and the main olfactory systems, and possibly other nasal chemosensory systems, play important roles in the copulatory responses of male hamsters to vaginal discharge.
Fast and loose covalent binding of ketones as a molecular mechanism in vertebrate olfactory receptors. Chemical production of selective anosmia
1984, TetrahedronOlfactory receptors undoubtedly have fast rates of association with odorant molecules. If the dissociation rate is also fast, the dissociation constant, Kd, will be comparatively large (≥10-6M). With such fast and loose binding, a receptor will recover function rapidly. If, on the other hand, the dissociation rate is slow, odorant binding will be tight, and the receptor will have slow recorvery. Previous investigators have explored tight binding (Kd≤10-8M). The present study is the first to probe the possibility of fast and loose binding in the olfactory epithelium of air-breathing vertebrates. Our approach is based on the conjecture that ketones are bound as Schiff bases (just as retinal is bound in visual pigment). As a model system, the Schiff base-forming bacterial enzyme acetoacetate decarboxylase (AAD) has been studied. Nucleophilic attack (e.g. BH4- reduction) of reversible AAD-carbonyl complexes produces irreversible binding to the active site in a fraction, φ, of the enzyme molecules. Kinetics are discussed and interpreted using the derived expression φ=1-[Kd/(Kd+S0)]m, where S0 is the initial concentration of carbonyl substrate and the exponent m is the ratio of the rate constant for attack of the protein-substrate complex to the rate constant for removal of substrate (e.g. by hypothesize attack of the free carbonyl). We hypothesize a similar pathway when the olfactory epithelium of experimental animals is treated with solutions of cyclohexanone or ethyl acetoacetate, in which Schiff base linkages are attacked in vivo by some endogenous nucleophile. We have developed a behavioral assay for olfactory receptor inactivation and report the first example of a chemically produced selective anosmia (odor blindness).
Perireceptor and receptor events in vertebrate olfaction
1984, Progress in NeurobiologyIn this article we have summarized the basic information which identifies several key issues in the study of perireceptor and receptor events in vertebrate olfaction. We have emphasized the biophysical and biochemical data which have established a pivotal role for the olfactory mucus in the access of odorants to receptor sites as well as their clearance from the micro-environment. In addition, based on initial reports in the literature, we have postulated that the uptake of odorants by cells in the olfactory epithelium and their subsequent enzymatic degradation is an important mechanism in odorant removal. Hence, the pre- and post-interactive events in vertebrate olfaction play a key role in molecular recognition, sensory transduction and receptor desensitization.
Study of the primary events in vertebrate olfaction is an increasingly active area of research in neurobiology. Application of contemporary techniques in cell and molecular biology as well as biochemistry and cellular biophysics is yielding new insights into the process and into establishing new hypotheses to be tested.
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This work was supported by the National Institutes of Health grant number NS 14773.
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Present address: Department of Chemistry, Princeton University, Princeton, NJ, U.S.A.