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PubMed2005

Morituri te salutant? Olfactory signal transduction and the role of phosphoinositides.

During the past 150 years, researchers have investigated the cellular, physiological, and molecular mechanisms underlying the sense of smell. Based on these efforts, a conclusive model of olfactory signal transduction in the vertebrate's nose is now available, spanning from G-protein-mediated odorant receptors to ion channels, which are linked by a cyclic adenosine 3',5'-monophosphate-mediated signal transduction cascade. Here we review some historical milestones in the chronology of olfactory research, particularly emphasising the role of cyclic nucleotides and inositol trisphosphate as alternative second messengers in olfactory cells. We will describe the functional anatomy of the nose, outline the cellular composition of the olfactory epithelium, and describe the discovery of the molecular backbone of the olfactory signal transduction cascade. We then summarize our current model, in which cyclic adenosine monophosphate is the sole excitatory second messenger in olfactory sensory neurons. Finally, a possible significance of microvillous olfactory epithelial cells and inositol trisphosphate in olfaction will be discussed.

Animals↗
PubMed1985

Rat trigeminal, olfactory and taste responses after capsaicin desensitization.

Experiment 1 showed that capsaicin injections severely reduced or eliminated nasal trigeminal responses to 3 odorants. Experiments 2 and 3 investigated whether desensitized animals could behaviorally detect and discriminate odors. Capsaicin treated animals had no measurable deficits in locating buried food, in odor aversion learning, or in operant odor detection and discrimination. Experiment 4 examined whether behavioral responsiveness to salty, sour and bitter tastes was affected by desensitization. Capsaicin injections did not affect responsiveness to salty or sour, but may have raised rejection thresholds for bitter. Broadly, the present results suggest that substance P-containing fibers mediate trigeminal responsiveness to odorants and irritants but that the loss of this responsiveness does not appreciably affect smell or taste, per se.

Animals↗
PubMed1989

Speech acceptability and olfaction in laryngectomees.

A number of hypotheses concerning the causal relationships and interrelationships between esophageal speech acceptability, olfactory abilities, and airflow volume in laryngectomees were tested. To assess the hypotheses, data were collected from 25 laryngectomees and comprised the following: (1) A measure of speech acceptability using a standard passage of prose; (2) odor identification test results in which 14 common odorants were used; (3) odor threshold test results in which an 11-step aqueous dilution series of l-butanol was used and: (4) a measure of nasal airflow volume in liters per minute. The null hypotheses linking speech acceptability, olfaction, and airflow volume were all tested and none of the path coefficients was significant. The results are discussed in relation to observations made by Gilchrist [Acta Otolaryngol. (Stockh.) 75:511-518 (1973)], who noted that those esophageal speakers who attained good speech maintained a greater sensitivity to smell. The findings in the present study do not support Gilchrist's observations.

Humans↗
PubMed1989

Olfaction through oral tracheal breathing tube.

Cancer of the larynx has approximately a 90% cure rate if detected early. Advanced lesions are treated surgically by removing the larynx and creating a stoma that joins the trachea. Although speech can be learned, the patient's ability to smell is permanently interrupted. This technique article describes fabrication of a simple device that permits olfaction by a laryngectomee.

Equipment Design↗
PubMed1985

Sex differences in odor identification ability: a cross-cultural analysis.

To ascertain the generality of a sex difference noted in odor identification ability, the University of Pennsylvania Smell Identification Test (UPSIT) was administered to four groups of subjects: Black Americans (n = 438), White Americans (n = 1559), Korean Americans (n = 106), and Native Japanese (n = 308). The women of all four groups outperformed the men to the same relative degree. The Korean American group performed better than the Black and White American groups, which, in turn, outperformed the Native Japanese. Analyses of the proportions of subjects correctly answering each of the test items revealed considerable similarity of relative item difficulty among the subject groups. Taken together, these data suggest that sex differences in odor identification ability are probably not due to ethnic or cultural factors, per se.

Adult↗
PubMed1988

Olfactory identification deficits in patients with focal cerebral excision.

The ability to identify common odors using the University of Pennsylvania Smell Identification Test was investigated in 120 patients with a focal surgical brain lesion and 20 normal control subjects. Results showed significant impairment after right or left temporal lobectomy, right or left frontal lobectomy, and right frontotemporal excision. Patients whose excision was confined to the left central, parietal or posterior area showed no significant deficit. The impairment after frontal lobectomy was demonstrated only in patients whose frontal-lobe removal invaded the orbital cortex; that group also showed a significantly greater impairment than did the temporal lobectomy group. All patient groups showed normal detection thresholds for n-butyl alcohol.

Adult↗
PubMed1993

Olfactory identification deficits in Down's syndrome and idiopathic mental retardation.

We investigated olfactory identification in children and adults with Down's syndrome (DS) and idiopathic mental retardation (IMR) and in age-matched normal controls (NC). Identification was assessed with a four alternative-forced-choice task modified from the University of Pennsylvania Smell Identification Test (M-UPSIT) and a yes/no task yielding measures of discrimination and response bias for the same stimulus material. Control tactile identification tasks were also administered. Results were that odor identification performance on both tasks was specifically impaired in DS compared to IMR and NC. Accuracy of identification on the M-UPSIT correlated inversely with age in DS only. When uncertain, DS and IMR subjects guessed "yes" more often than "no" on the Yes/No task (liberal decision bias) and guessed the last response alternative on the M-UPSIT (recent position bias), whereas the normal subjects had neutral decision bias on the Yes/No task and matched the objective position presentation probabilities on the M-UPSIT. Decision bias correlated with accuracy of identification in both tasks for the DS subjects only.

Adolescent↗
PubMed1994

Olfactory lateralization in the chick.

Chicks using their right nostril (and so with direct olfactory input to the right hemisphere), and presented simultaneously with two objects identical in visual appearance with the rearing object, and differing only in odour, chose that which smelled like the rearing object. Chicks using the left nostril chose equally readily but at random. Earlier work, using similar tests, has shown special interest of the right hemisphere in change in visual properties of familiar stimuli, suggesting that analysis of a wide range of properties of a familiar stimulus may be an important function of the right hemisphere in the chick, with consequent detection of novelty.

Animals↗
PubMed1979

A study of olfaction and gustatory senses in sheep after olfactory bulbectomy.

The importance of taste and smell in discrimination of sodium salts was examined in normal and anosmic sheep. To test for anosmia, faeces of pig, calf and sheep were used as noxious odours. Intact sheep, and sheep with one olfactory bulb removed avoided the aversive stimulus whereas following total bulbectomy, the faecal odour was no longer a deterrent. Olfactory bulbectomy did not affect food intake but changes in fluid intake, urinary loss and electrolyte excretion were apparent. In two-choice preference tests, normal sheep showed a marked aversion for 0.48 M NaHCO3 and 0.51 M NaCl when compared to water. Following either unilateral or bilateral olfactory bulbectomy the aversion for sodium salts persisted but was less extreme. This suggests that in the final discrimination of sodium salts the sense of taste is dominant but olfaction or the olfactory bulb may have a minor role.

Animals↗
PubMed1983

Maternal behavior priming in virgin and caesarean-delivered Long-Evans rats: effects of brief contact or continuous exteroceptive pup stimulation.

The effects of 8 days of prior exposure to pups (Priming) in the form of continuous exteroceptive (smell, sight and sound), or 15 min/day physical access (taste and touch possible) stimulation on the subsequent latency to become maternal during cohabitation with pups (concaveation) was studied in Long-Evans female rats. Brief daily access was effective in hastening the onset of maternal behavior only in those virgins which engaged in pup licking during Priming and in maintaining short-latency maternal responsiveness only in those day 21 pregnancy-terminated, thelectomized rats which initiated maternal behavior during Priming. Exteroceptive stimulation was ineffective in both virgins and caesarean-sectioned rats. These findings stress the importance of physical interactions with pups (unrelated to nipple stimulation) for the development of nurturance.

Animals↗
PubMed1988

Sensory stimulation and energy density in the development of satiety.

To determine the contribution of sensory stimulation to the changing hedonic response to foods, the effects of consuming very low-calorie and higher calorie versions of soup and jello on the subjective pleasantness of foods were compared. Subjects were 24 normal weight females with low dietary restraint. Half the subjects were given test meals of low- and high-calorie tomato soup and half were given low- and high-calorie orange jello. They rated the pleasantness of the appearance, smell, texture and taste of nine sample foods as well as hunger and stomach fullness before and 2, 20, 40 and 60 min after consumption of the test meal. After the 60 min rating subjects were offered as much as they wanted to eat of a second course of cheese on crackers. Despite differences in the energy density of the test meals, there were no significant differences in the weights of food eaten in either the first or second course and no significant compensation in the second course for the energy differences of the first course. No differential effects of the caloric manipulation were observed in terms of hunger or fullness or in the development, time course and magnitude of sensory-specific satiety. That very low-calorie foods can produce sensory-specific satiety indicates that the sensory properties of foods are important for the changing hedonic response to foods as they are consumed.

Adolescent↗
PubMed1989

Olfactory coding in the monkey lateral hypothalamus: behavioral and neurochemical properties of odor-responding neurons.

The activity of glucose-sensitive (GS) and glucose-insensitive (GIS) neurons was recorded in the lateral hypothalamic area (LHA) of monkeys during olfactory stimulation, a conditioned alimentary bar press task, and microelectrophoretic application of catecholamines. Olfactory stimuli evoked response of 88% of the GS neurons, and 52% of the GIS cells responded to odors. The GS neurons were more broadly tuned across odorants than the GIS cells, and their responses to various smells with distinct hedonic value were also differential. The odor-responding GS neurons were depressed during the bar press and reward periods of the task, and were mainly inhibited by dopamine. The odor-responding GIS cell activity increased in response to cue light and tone, and was facilitated by dopamine. Histological examinations disclosed topographic dissociation of the odor-responding GS and GIS cells: the former were located in more ventromedial regions than the latter. The results indicate that the GS neurons integrate multiple chemosensory inputs from both endogenous and exogenous sources in the regulation of feeding: whereas the GIS cells distinguish among fewer, more specific cues to control food acquisition behavior.

Animals↗
PubMed1991

Peripheral anosmia attenuates female-enhanced aggression in male rats.

It is well established that male rats with prior access to sexually active females show enhanced offensive aggression toward unfamiliar male intruders. The present study assessed the importance of the sense of smell for this facilitatory effect. It was found in 2 independent experiments that anosmia, induced peripherally by surgically removing the olfactory epithelium and cutting the olfactory nerves, reduced baseline levels of offensive aggression and significantly attenuated the female-enhanced aggression effect. It was also found that sexual performance of anosmic rats was context-dependent, in that it was more impaired in the homecage environment than in standard observation cages. In contrast to sham-operated males, the experimental animals showed no preference for estrous over anestrous females in a mate choice test. Anosmic males did not appear more fearful than controls, as assessed in a hyponeophagia test, but they showed less exploratory behavior (rearing and head-dipping) in the hole-board test, and less rearing activity in automated activity boxes.

Aggression↗
PubMed1993

Effect of flavor enhancement of foods for the elderly on nutritional status: food intake, biochemical indices, and anthropometric measures.

The irreversible declines in taste and smell acuity that occur in many elderly persons can contribute to inadequate food intake and nutrition that are prevalent among the aged. Although chemosensory deficits cannot be reversed, previous studies have shown that the addition of intense flavors to foods can compensate for perceptual losses and improve food palatability and acceptance. In this study, the effect of sustained (3 week) flavor enhancement of typical institutional foods on the diet, health, and well being of 39 elderly (average age 84.6 SE 0.81 years) retirement-home residents was evaluated. For 3 weeks subjects ate an institutional diet (unenhanced). During another 3-week period, the same subjects ate identical foods to which intense flavors were added (enhanced). The 39 subjects were tested in two groups. For group 1 the unenhanced food period preceded the enhanced food period. For group 2, the order was reversed. Food intake was measured every weekday throughout the study, and the nutritional composition of the diet was analyzed. Biochemical measures of health status were obtained at the beginning of the study (baseline) and following both the unenhanced and enhanced periods. These measures included somatomedin-C/insulin-like growth factor I, transferrin, total T- and B-lymphocytes, and routine blood chemistries. Weight, height, midarm circumference, and triceps skinfold thickness were also measured. Handgrip strength and pinch strength were measured in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Context conditioning: positive reinforcing effects of various food-related stimuli.

Rats were subjected to context preference tests to investigate the degree to which various manipulations involving food stimuli can be used to appetitively condition contextual cues. One manipulation consisted of placing hungry rats in a context that contained food that they could consume. A second one involved exposure to a context containing food that could only be seen and smelled, without consumption being possible. A third type of manipulation consisted of exposing animals to a context after the consumption of a small meal in the home cage. Finally, hungry, control subjects were merely exposed to a context containing an empty food tray. Preference for the context was only enhanced after the first type of manipulation, indicating that the actual consummatory act constitutes the major source of reinforcement in the present procedure. Olfactory and visual food cues, as well as postingestional aftereffects in isolation, did not function as reinforces.

Animals↗
PubMed1995

Twin analysis of odor identification and perception.

Findings from the first twin analysis using the University of Pennsylvania Smell Identification Test (UPSIT) and a phenyl ethyl alcohol (PEA) threshold detection test are presented. A genetic influence on odor identification was suggested for males, but not for females, consistent with previous twin research on physical measures. In addition, females scored significantly higher on the UPSIT than males. A curvilinear age trend for odor identification was detected for males, but not for females. In contrast, neither genetic, age, nor gender effects were suggested for PEA sensitivity. Performance on the olfactory tests was unrelated to scores on standard measures of intelligence.

Adolescent↗
PubMed1988

Degeneration and regeneration of the olfactory epithelium following inhalation exposure to methyl bromide: pathology, cell kinetics, and olfactory function.

The effects of acute inhalation exposure to methyl bromide (MeBr) on the olfactory epithelium of male F-344 rats was investigated by morphologic examination of animals killed at varying timepoints during and following exposure to 200 ppm MeBr 6 hr/day for 5 days. Cell replication rate and histopathology were used to assess the kinetics of repair. In addition, olfactory function, using the buried food pellet test, was assessed and the result compared with morphological recovery. Extensive destruction of the olfactory epithelium was evident in animals killed directly after a single 6-hr exposure to MeBr. Histologic features of these lesions indicate that the primary, or most severe, effect of MeBr exposure was on the sustentacular cells and mature sensory cells; basal cells were generally unaffected. By Day 3, despite continued exposure, there was replacement of the olfactory epithelium by a squamous cell layer that increased in thickness and basophilic cytoplasmic staining over the next 2 days of exposure. One week postexposure, the epithelial region was covered by a layer of polyhedral, basophilic cells, and from 2 to 10 weeks postexposure, the epithelium exhibited progressive reorganization to reform the original olfactory epithelium pattern. By Week 10, 75-80% of the olfactory epithelium appeared morphologically normal. Cell replication showed a single peak of olfactory epithelial cell proliferation at Day 3 of exposure, with a labeling index of 14.5% compared to 0.7% in controls. Cell replication rates returned gradually to control levels by Week 10 postexposure. Behavioral tests of olfactory function in animals after a single 6-hr exposure to 200 ppm MeBr demonstrated a loss of the sense of smell, with recovery of this function by Day 6. Exposure to 90 ppm caused no observable effect on olfactory function or morphology. These findings demonstrate that the olfactory mucosa is highly sensitive to the toxic effects of MeBr and that olfactory epithelial cell proliferation, and possible regeneration, begins and occurs rapidly even in the face of continued exposure. Cell replication was most prominent in the layer of basal cells adjacent to the basal lamina, supporting proposals by other workers that the progenitors of both sustentacular cells and neurons reside in this location. Of interest is the fact that functional recovery occurs prior to complete morphological reorganization, indicating the shortcoming of utilizing olfactory morphology as an index of functional integrity.

Administration, Inhalation↗
PubMed1993

Odorant-selective genes and neurons mediate olfaction in C. elegans.

Olfaction is a versatile and sensitive mechanism for detecting volatile odorants. We show that the nematode C. elegans detects many volatile chemicals, which can be attractants, repellents, or attractants at low concentrations and repellents at high concentrations. Through laser ablation, we have identified chemosensory neurons that detect volatile odorants. Chemotaxis to volatile odorants requires different sensory neurons from chemotaxis to water-soluble attractants, indicating that C. elegans might have senses that correspond to smell and taste, respectively. Single neurons have complex sensory properties, since six distinguishable volatile odorants are sensed by only two types of sensory neurons. Chemotaxis to subsets of volatile odorants is disrupted by mutations in the odr genes, which might be involved in odorant sensation or signal transduction.

Animals↗