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M M Mozell

Publications and source records attributed to M M Mozell.

At least 19 recordsLinked to original sources

The recording of odorant-induced mucosal activity patterns with a voltage-sensitive dye.

1. Fluorescence changes in the dye (WW 781) were monitored at 100 contiguous sites in a 10 x 10-pixel array on the bullfrog and salamander olfactory mucosas every 10 ms in response to odorous stimuli. The odorants were d-limonene, butanol, and amyl acetate, each presented at two concentrations with a 3:1 ratio. 2. The fluorescence signals elicited by these odorous stimuli were nearly identical in shape and time course to the electro-olfactograms (EOGs) recorded from the same animal under identical conditions. Like the EOGs, the fluorescence signals exhibited adaptation and were abolished by both Triton X-100 and ether. There was no measurable fluorescence when the tissue was not stained with the dye, and there was no change in fluorescence when, for stained tissue, nonodorized, humidified air was presented as the stimulus. 3. This technique presumably monitors the same events as the EOG, but has the advantage of simultaneously recording the odorant-induced activity from multiple sites across most of the mucosa. Thus this technique preserves subtle differences heretofore lost by other techniques both in the coarseness of their matrices and in the variability generated by trying to piece together, into one collage, results from numerous presentations given at different times. 4. In all preparations, there was a larger difference in the inherent activity patterns (derived from response magnitudes) between different odorants than between different concentrations of the same odorant. These differences were largest on the mucosa lining the floor of salamander's olfactory sac. d-limonene and butanol gave their largest responses near the internal and external nares, respectively, whereas the responses for amyl acetate were more uniform across the mucosal sheet. In contrast to the salamander, smaller differences were observed for both the roof and the floor of the bullfrog's olfactory sac. For the floor, both amyl acetate and d-limonene elicited similar patterns of response magnitude, whereas butanol differed from each of these odorants by eliciting a larger response on the anteriolateral aspect of the mucosa and a lesser response on the remainder. For the roof, different odorants produced different activity patterns, which had profiles not simply described as regions of maximal and minimal responsiveness. 5. Different inherent activity patterns based on temporal characteristics of the fluorescence responses were also observed for different odorants. Each odorant produced a different pixel-by-pixel pattern for the times at which the responses started and ended. For any given odorant, these temporal patterns paralleled the patterns given by response magnitudes.(ABSTRACT TRUNCATED AT 400 WORDS)

Ambystoma

Successful treatment of phantosmia with preservation of olfaction.

A 26-year-old woman had an 8-year history of phantosmia in her left nostril. The phantosmia could be eliminated by nostril occlusion or cocainization of the olfactory epithelium on the involved side. Because her symptoms and testing suggested a peripheral problem, a full-thickness "plug" of olfactory epithelium from under the cribriform plate (including all the fila olfactoria) was excised. At 5 weeks postoperatively, the phantosmia was completely gone, and her olfactory ability had returned to preoperative levels. Either the removal of abnormal peripheral olfactory neurons from the nose or the interruption of incoming signals to the olfactory bulb eliminated the phantosmia. This form of therapy for phantosmia offers an alternative to more radical procedures such as olfactory bulbectomy and may offer a significant sparing of olfactory ability.

Adult

Determination of carbon dioxide detection thresholds in trained rats.

Concentration-response functions for the detection of CO2 were established for six rats. The animals were tested in a wind tunnel apparatus and trained using standard operant techniques and a discrete trials, go, no-go successive discrimination paradigm. The primary conclusion to be drawn from the performance measurements is that, at least under carefully controlled conditions, rats can detect physiologic concentrations of CO2 (0-4%). Minimum detectable concentrations fell within the range of 0.04-1.7% CO2. The concentration-response function describing the detectability of CO2 for the six rats was divided into an upper and lower limb at a concentration (5%) that was approximately equal to the end expiratory CO2 levels for the rat (4.88%). High levels of performance were observed for concentrations above this point, while those below it (0.02-2.5%) represented the dynamic range of detectability. Based on a 65% performance criterion, the average threshold performance for six rats was 0.52%. Possible interpretations of these data are discussed.

Animals

Odorant identification in rats: an update.

In a previous report, Youngentob et al. (8) described a new and substantially different type of animal psychophysical procedure in which rats were trained to differentially report (i.e., identify) five different odorants. The present study confirms and extends the usefulness of the cross-modal association paradigm as an effective means for developing an extensive nonverbal "vocabulary" with which an animal can communicate multiple changes in sensory stimuli. Given the appropriate nonverbal means of communication, a rat has the channel capacity to differentially report (i.e., identify), at least ten different odorants. The expansion to a ten odorant identification task is discussed with respect to the analytic capabilities of the animal model for the study of olfactory quality perception.

Algorithms

Fish-odor syndrome presenting as dysosmia.

We describe a patient who had perceived an unpleasant odor or taste for at least 20 years. Several other physicians had unsuccessfully treated her for infections, mucus membrane dryness and inflammation, chronic tonsillitis, and psychiatric disorders. Her workup at the State University of New York Health Science Center at Syracuse Olfactory Referral Center included a thorough history, examinations (including endoscopic studies of her nose, pharynx, and lungs), roentgenograms, taste testing, olfactory testing, and selective anesthesia of her chemosensory areas. The perception occurred only during exhalation, and appeared to be binasal. These findings, together with her morning mucus sample having a strong fishlike odor, prompted us to suspect a metabolic problem. Further testing at the Monell-Jefferson Chemosensory Clinical Research Center, Philadelphia, Pa, confirmed that she had trimethylaminuria. It is important to consider this and other treatable conditions when evaluating individuals with olfactory complaints.

Adult

A method for establishing a five odorant identification confusion matrix task in rats.

Using a cross-modal association paradigm, rats were trained to associate a particular tunnel and response location with one of five different odorants (isoamyl acetate, propyl acetate, acetic acid, phenethyl alcohol, and anethole). Each of the five tunnels differed with respect to: 1) the illuminated pattern on the response key; 2) the brightness of the illuminated pattern; and 3) the somesthetic quality of the tunnel floor. Standard operant techniques were used to train trial initiating and sampling behavior at a central odorant presentation point. Following acquisition training, the animals were tested using a standard 5 X 5 confusion matrix design. The results showed for the first time that rats are capable of performing, with a high degree of accuracy, an odorant identification confusion matrix task analogous to humans. Furthermore, using multidimensional scaling techniques, these data represent the first instance in which the perceptual odor space of an animal can be determined. With the animal model in hand, we can begin to examine how, in the presence of neural dysfunction, one odorant may be correctly identified as another.

Animals

The biophysics of nasal airflow.

The biophysics of nasal airflow involve the measurement, analysis, and understanding of bulk airflow or momentum transport through the nasal cavity and of the exchange of mass and heat laterally between the air stream and the walls. In both of these areas, optimal progress depends on judicious, combined, and continuous use of physical models, mathematical calculations, and measurements made on human subjects. The progress that has been made to date is both fascinating and encouraging and suggests that great improvement in understanding, diagnosis, and treatment of nasal and upper airway disease will be possible in the future through closer contact and cooperation between clinicians and physical and biological scientists.

Airway Resistance

Olfactory mucosa/air partitioning of odorants.

The present study evaluates the contribution of the receptor cell compartment to the total mucosal odorant uptake. Using radioactive odorants, partition coefficients for normal bullfrog olfactory mucosa were compared to the partition coefficients from mucosa in which the receptor cells had been removed by cutting one of the olfactory nerves and allowing two weeks for complete degeneration. For the more water-soluble odorants (butanol and isobutyric acid), both sides sorbed the same amount of odorant, suggesting that the mucosal uptake mostly reflects uptake by the water in the mucosa. For the less water soluble odorants (octane and amyl acetate), the uncut side did sorb significantly more odorant than the cut side.

1-Butanol

Airflow patterns in a human nasal model.

Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

Catheterization

A quantitative analysis of sniffing strategies in rats performing odor detection tasks.

The sniffing strategies of rats performing two learned odor detection tasks were monitored with a pneumotachograph and quantitatively analyzed with respect to fifty-two characteristics. The results of this study demonstrated that the rat's sniffing varied for different odorants, different concentrations of the same odorant, and between air and odor trials. The variations resulted from changes in such descriptors as volume, duration, average flow rate, peak flow rate and sniff number. In general, a sniffing pattern began with one or two inspirations followed by alternating inspirations and expirations. Comparison of earlier and later sniffs in a bout demonstrated a growth towards both a maximum inspiratory and expiratory sniff which had the largest duration, volume, average flow rate and peak flow rate. These maximum sniffs occurred at or near the end of a bout. Although analysis of the fifty-two characteristics was quantitatively useful in determining the physiologic values and airflow patterns generated by sniffing, a single univariate response measure incorporating twelve characteristics was the best descriptor of how sniffing patterns varied with odorant stimuli.

Animals

"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.

Acyclic Monoterpenes

Improvement of olfaction in laryngectomized patients with the larynx bypass.

Hyposmia following laryngectomy is an often recognized phenomenon. A larynx bypass device was used to determine whether this olfactory deficit could be reversed simply by restoring nasal airflow. Odorant detection thresholds and confusion matrix identification tests were administered to laryngectomy and normal comparison groups. Data on nasal airflow characteristics with and without the bypass were also analyzed. The results suggested that restoration of nasal airflow completely reversed the hyposmia for trigeminal nerve stimuli. However, the reversal of hyposmia was not complete for those odorants which primarily, if not exclusively, stimulate the olfactory nerve. This suggested that other factors may contribute to laryngectomy-induced hyposmia for olfatory nerve stimuli. Additionally, nasal airflow analysis revealed that confusion matrix identification scores were depedent upon inspiratory sniff flow rates with and without the larynx bypass. It is argued that rehabilitation for the laryngectomee should include efforts to restore and maintain preoperative olfactory acuity.

Adult

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.

Animals

A parametric study of the stimulation variables affecting the magnitude of the olfactory nerve response.

The magnitude of olfactory responses can be related to three primary variables [number of odorant molecules (N), sniff volume (V), and sniff duration (T)] and three derived variables [concentration (C = N/V), flow rate (F = V/T), and delivery rate (D = N/T)]. To evaluate the effects of these interdependent variables upon the olfactory response, the summated multiunit discharges were recorded from the olfactory nerves of nine frogs in response to octane presented at two levels (in 2:1 ratio) of each primary variable. This presentation defined eight "sniff" combinations representing three levels of each derived variable. In an ANOVA of the logs of the responses, the effect of each primary variable was highly significant, with no significant interactions. A multiplicative regression model incorporating the effects of the three primary variables represented responses exceedingly well, with positive effects of N and T and a negative effect of V. When, with this model, the effect of each of the derived variables was isolated from the effects of all other variables, the analysis showed a positive effect for C, a near-zero positive effect for D, and a negative effect for F. Placing certain constraints upon the model parameters generates 13 distinct one- and two-variable models (e.g., the [C, T] model requires N and V to have equal but opposite effects). In ranking these reduced models in terms of their ability to predict the neural response, the predictive ability of [F, N] and [C, T] was at least as good as that of the three-variable model.

Analysis of Variance

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.

Adsorption

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.

Animals