"Imposed" and "inherent" mucosal activity patterns. Their composite representation of olfactory stimuli

Both regional differences in mucosal sensitivity and a gas chromatography-like process along the mucosal sheet have been separately proposed in two sets of earlier studies to produce different odorant-dependent activity patterns across the olfactory mucosa. This investigation evaluated, in one study, whether and to what degree these two mechanisms contribute to the generation of these activity patterns. Summated multiunit discharges were simultaneously recorded from lateral (LN) and medial (MN) sites on the bullfrog's olfactory nerve to sample the mucosal activity occurring near the internal and external nares, respectively. Precisely controlled sniffs of four odorants (benzaldehyde, butanol, geraniol, and octane) were drawn through the frog's olfactory sac in both the forward (H1) and reverse (H2) hale directions. By combining the four resulting measurements, LNH1, LNH2, MNH1, and MNH2, in different mathematical expressions, indexes reflecting the relative effects of the chromatographic process, regional sensitivity, and hale direction could be calculated. Most importantly, the chromatographic process and the regional sensitivity differences both contributed significantly to the mucosal activity patterns. However, their relative roles varied markedly among the four odorants, ranging from complete dominance by either one to substantial contributions from each. In general, the more strongly an odorant was sorbed by the mucosa, the greater was the relative effect of the chromatographic process; the weaker the sorption, the greater the relative effect of regional sensitivity. Similarly, the greater an odorant's sorption, the greater was the effect of hale direction. Other stimulus variables (sniff volume, sniff duration, and the number of molecules within the sniff) had marked effects upon the overall size of the response. For strongly sorbed odorants, the effect of increasing volume was positive; for a weakly sorbed odorant, it was negative. The reverse may be true for duration. In contrast, the effect of increasing the number of molecules was uniformly positive for all four odorants. However, there was little evidence that these other stimulus variables had a major influence upon the effects of the chromatographic process and regional sensitivity differences in their generation of mucosal activity patterns.     

Modeling inspiratory and expiratory steady-state velocity fields in the Sprague-Dawley rat nasal cavity

Distribution patterns of odorant molecules in the rat nasal olfactory region depend in large part on the detailed airflow patterns in the nasal cavity, which in turn depend on the anatomical structure. To investigate these flow patterns, we constructed an anatomically accurate finite element model of the right nasal cavity of the Sprague-Dawley rat based on horizontal (anterior-posterior) nasal cast cross sections. By numerically solving the fluid mechanical momentum and continuity equations using the finite element method, we studied the flow distribution and the complete velocity field for both inspiration and expiration throughout the nasal cavity under physiological flow rates of resting breathing and sniffing. Detailed velocity profiles, volumetric flow distributions, and streamline patterns for quasi-steady airflow are presented. S-shaped streamlines passing through the olfactory region are found to be less prevalent during expiratory than inspiratory flow leading to trapping and an increase in odorant molecule retention in the olfactory region during sniffing. The rat nasal velocity calculations will be used to study the distribution of odorant uptake onto the rat olfactory mucosa and compare it with the known anatomic location of some types of rat olfactory receptors.     

Evidence for a Chromatographic Model of Olfaction

The gradient of activity produced along the olfactory mucosa by odorant stimulation was measured by the ratio (the LB/MB ratio) of the summated neural discharges recorded from two branches of the olfactory nerve, a lateral branch (LB) supplying a mucosal region near the internal naris and a medial branch (MB) supplying a region near the external naris. Twenty-four frogs "sniffed" sixteen different odorants, each odorant at four concentrations and two flow rates. Increases in concentration and flow rate produced statistically reliable increases in the ratios; the magnitude of these increases was considerably smaller than the magnitude of the statistically significant changes that could be achieved by shifting the odorants themselves. Even the small change due to concentration depended upon the odorant presented. Thus, even at the highest physiologically possible concentrations and flow rates, the general level of the activity gradient along the mucosa appeared to be determined mainly by the particular odorant used. The relative retention time of each of these 16 different odorants was measured in a gas chromatograph fitted with a Carbowax 20M column. In general, the longer the odorant's retention time the smaller its LB/MB ratio. This suggests that the different mucosal gradients of activity are established for different odorants by a chromatographic process. The data further suggest that the mucosa behaves like a polar chromatographic column.     

Electrophysiological evidence for a topographical projection of the nasal mucosa onto the olfactory bulb of the frog

Three olfactory nerve branches respectively subserving either a medial, an intermediate, or a lateral region of the dorsal olfactory receptor sheet of the bullfrog Rana catesbeiana were electrically stimulated with bipolar platinum hook electrodes. Extracellular single unit responses from 93 second-order cells in different regions of the olfactory bulb were recorded with metal-filled glass micropipets. The excitatory responsiveness of each unit to the stimulation of each of the three nerve branches (response profile) was determined. Some units were sensitive to stimulation of each of the three nerve branches, thus suggesting a wide projection from the entire receptor sheet. On the other hand, other units were more selective. Of this latter group, units in the lateral bulb were excited by nerve branches subserving the more lateral regions of the receptor sheet; units in the medial bulb were excited by the nerve branches subserving the more medial regions of the receptor sheet. These data provide electrophysiological evidence for a topographical projection of the olfactory receptor sheet onto the olfactory bulb, and further suggest that the projections onto different bulbar cells vary in degree of localization.     

The effect of flow rate upon the magnitude of the olfactory response differs for different odorants

The authors wish to bring to your attention that the valuesgiven in Table II for stimulus volume, which are listed in cm³in the column headed by V, were clerically misstated and didnot agree with the values given in the text. None of the othervalues in the article or any of its reported findings and interpretationswere affected by this clerical error. The correct values forthis column from top to bottom should have read in cm³ as follows:0.405, 0.70, 1.28, 2.20, 0.405, 0.70, 1.28, 2.20, 0.405, 0.70,1.28, 2.20, 0.405, 0.70, 1.28, 2.20, 0.405, 0.70, 1.28, 2.20,0.405, 0.70, 1.28, 2.20.     

The effect of flow rate upon the magnitude of the olfactory response differs for different odorants

There are discrepancies in the literature as to whether increasingsniff flow rate increases or decreases the magnitude of theolfactory response. Earlier work from this laboratory suggestedthat the size and sign of the effect of flow rate might dependupon how strongly the odorant presented sorbs to the mucosa.To pursue this possibility the summated multi-unit dischargeswere recorded from two sites on the olfactory nerve samplingwidely separated upstream and downstream regions along the flowpath of the bullfrog's olfactory mucosa. Artificially producedsniffs were presented at four flow rates for each of six odorantsrepresenting a wide range of mucosal sorption strengths. Theresults showed a distinct relationship between the effect offlow rate and the sorption strength of the odorant presented,going from a negative effect for the weakly sorted odorantsto highly positive effects for the strongly sorbed odorants.Furthermore, as expected if the flow rate effect depends uponsorption, the strongly sorbed odorants gave more positive flowrate effects as the mucosal surface over which their moleculesflowed increased. Apparently, then, the effect of flow rateon the magnitude of the olfactory response can range from negativeto markedly positive depending upon how strongly the odorantin question sorbs to the mucosa.     

Effect of Nasal Dilators on Perceived Odor Intensity

Subjects wearing nasal dilators rated olfactory stimuli as beingmore intense compared with ratings done without nasal expansion.The results support a perceptual constancy model in olfaction.Chem. Senses 22: 177–180, 1997. ¹Present address: Biology Department, St Lawrence UniversityCanton, NY 13617, USA ²Present address: PO Box 802, Drew University, Madison, NJ 07940,USA     

Factors influencing the differential sorption of odorant molecules across the olfactory mucosa

By use of a flow dilution olfactometer, tritium-labeled odorants were presented through the external naris to the bullfrog's intact olfactory sac. After stimulation the animal was frozen in liquid nitrogen. The dorsal surface and eminentia of the olfactory sac were then removed and sawed into sections perpendicular to the long axis of the mucosal surface. Each section was dissolved in a tissue solubilizer and counted in a liquid scintillation system. The amount of radioactivity in each section was used to estimate the number of odorant molecules it sorbed. For tritiated butanol there was a significant decrease in radioactivity from the section containing the external naris to that overhanging the internal naris. The steepness of the gradient was unaffected by a rather large range of stimulus flow rates, volumes, and partial pressures. Only when these parameters were pushed to extreme physical limits did this gradient change significantly. When the stimulus was presented through the internal rather than the external naris, the butanol gradient reversed its direction, decreasing from the internal to external. Unlike butanol, tritiated octane presented through the external naris was rather evenly distributed among the mucosal sections. That is, octane showed no distribution gradient across the mucosa. These results complement previous electrophysiological data that suggested a "chromatographic-like" differential sorption of odorant molecules across the mucosa.     

Numerical modeling of odorant uptake in the rat nasal cavity

An anatomically accurate 3-dimensional numerical model of the right rat nasal cavity was developed and used to compute low, medium, and high flow rate inspiratory and expiratory mucosal odorant uptake (imposed patterning) for 3 odorants with different mucus solubilities. The computed surface mass flux distributions were compared with anatomic receptor gene expression zones identified in the literature. In general, simulations predicted that odorants that were highly soluble in mucus were absorbed dorsally and medially, corresponding roughly to receptors from one of the gene expression zones. Insoluble odorants tended to be absorbed more peripherally in the rat olfactory region corresponding to the other 2 zones. These findings also agreed in general with the electroolfactogram measurements and the voltage-sensitive dye measurements reported in the literature. This numerical approach is the first to predict detailed odorant flux information across the olfactory mucosa in the rat nasal cavity during inspiratory and expiratory flow and to relate it to anatomic olfactory receptor location, physiological function, and biochemical experiment. This numerical technique can allow us to separate the contributions of imposed and inherent patterning mechanisms on the rat olfactory mucosa.     

Olfactory stimulation variables. Which model best predicts the olfactory nerve response?

Mozell et al. (1984. J. Gen. Physiol. 83:233-267) have examined the traditional manner in which olfactory stimulus-response relationships have been addressed. They developed a model that describes the olfactory nerve response as a function of three factors, viz., the number of odorant molecules (N), the stimulus duration (T), and the stimulus volume (V). In addition, two models derived from this three-variable model were also found to predict the response well. These were the [F, N] model involving flow rate (F = V/T) and, ranking closely behind, the [C, T] model involving concentration (C = N/V). A model involving the delivery rate (D = N/T) and volume was found to predict the response poorly. These models imply very different stimulus-response relationships. The present study was designed to assess the validity of this earlier approach by testing specific predictions drawn from each of the models. Because of the excellence of the [F, N] model, one would predict that the response will not change when F and N are held constant in spite of proportional increases in V and T. Similarly, one would predict from the [C, T] model that the response will be constant when C and T are held constant in spite of proportional increases in N and V. Because of the poor showing of the [D, V] model, one would predict changes in the response even when D and V are held constant while N and T are increased proportionately. It was observed that when F and N were held constant, the response was, in fact, constant. When D and V were held constant, the response increased dramatically. When C and T were held constant, there was a statistically significant, but small, change in the response. These results support the approach taken by Mozell et al. (op. cit.) and highlight the applicability of the [F, N] model to peripheral olfactory processing. The results are discussed in terms of their impact on the traditional manner in which olfactory stimulus-response relationships are conceived.