We have developed a strategy for the rapid high-throughput screening of odor responsivity in genetically altered mice (in fact, any experimentally altered animal). Specifically, the report presents the development and validation of a fully automated procedure based on the evaluation of an animal's stimulus-induced reflexive breathing response (i.e. sniffing behavior) to both air and odorant stimuli. The method requires no training of the animal to be screened and the outcome of the evaluation yields an operationally defined measure. Briefly, using whole-body plethysmography, the procedure determines the numerical values for a set of 14 respiratory measures in response to the presentation of air and a well-above-threshold concentration of the odorant propanol. These measures of stimulus-induced sniffing are incorporated into a model that defines a single univariate measure of response behavior, or 'Sniffing Index', for each screened animal. The approach significantly discriminated between the reflexive sniffing response of a control group of mice and that of an experimentally defined manipulated group for which, a priori, we expected to observe a robust altered breathing response to odorant stimulation (i.e. non-odor-aversion-conditioned versus odor-aversion-conditioned C57BL/6J mice). Further, the procedure was able to significantly discriminate between a mutant phenotype with documented alterations in physiologic and behavioral function (namely, the OMP-null mutant), and their background strain. In addition, applying epidemiologic screening principles to the observed data, we established an operational procedure for the evaluation of unknown animals.
Viral upper respiratory infections are the most common cause of clinical olfactory dysfunction, but the pathogenesis of dysosmia after viral infection is poorly understood. Biopsies of the olfactory mucosa in patients that complain of dysosmia after viral infection fall into two categories: one in which no olfactory epithelium is seen and another in which the epithelium is disordered and populated mainly by immature neurons. We have used intranasal inoculation with an olfactory bulb line variant of MHV to study the consequences of viral infection on peripheral olfactory structures. MHV OBLV has little direct effect on the olfactory epithelium, but causes extensive spongiotic degeneration and destruction of mitral cells and interneurons in the olfactory bulb such that the axonal projection from the bulb via the lateral olfactory tract is markedly reduced. Moreover, surviving mitral cells apparently remain disconnected from the sensory neuron input to the glomerular layer, judging from retrograde labeling studies using Dil. The damage to the bulb indirectly causes a persistent, long-term increase in the turnover of sensory neurons in the epithelium, i.e. the relative proportion of immature to mature sensory neurons and the rate of basal cell proliferation both increase. The changes that develop after inoculation with MHV OBLV closely resemble the disordering of the olfactory epithelium in some patient biopsies. Thus, damage to the olfactory nerve or bulb may contribute to a form of post-viral olfactory dysfunction and MHV OBLV is a useful model for studying the pathogenesis of this form of dysosmia.
To test the hypothesis that odorant quality perception is altered in olfactory marker protein (OMP)-null mice, we trained and tested adult OMP-null and control mice, using a 5-odorant identification confusion matrix task (animal odorant confusion matrix [AOCM]). On average, control and null mice performed the task at equivalent levels. The composite 5 x 5 response matrix from 40 testing sessions for each subject (both OMP-null and control) was compared with that of every other subject, yielding a dissimilarity matrix of AOCM responses. A multidimensional scaling (MDS) analysis of the dissimilarity data yielded a 4-dimensional solution, with each mouse occupying a point in MDS animal space. Statistical analysis demonstrated significant effects of genotype in determining the location of a mouse in the MDS space. These data suggest, therefore, that compared with that of controls, odorant quality perception is altered in the OMP-null mouse.
Abstract The ability to detect and interpret the chemicals in our environment affects nearly every aspect of our survival. The flavor of our food, i.e., the combination of its taste and smell, is used both to prompt ingestion of nutrients and to protect us from ingesting or inhaling toxins. In the study of taste and olfaction, there are certain as yet unresolved questions that date from the very earliest research into these areas. For example, there is continued debate on the nature of primary stimuli, on the mechanisms of transduction, and on the ways in which stimuli are encoded and interpreted by the nervous system. In this review, the current thinking about these questions, as well as some recent data that may help to resolve them, are outlined. Data from both animal and human models are used to show how technological advances, particularly in the realm of molecular neurobiology, are providing the tools for a new and more complete understanding of how we taste and smell the chemicals in our environment.
Background: Gestational ethanol exposure enhances the adolescent reflexive sniffing response to ethanol odor. Postnatal exposures of naïve animals as either an observer (i.e., conspecific) or demonstrator (i.e., intoxicated peer) using a social transmission of food odor preference paradigm also yields enhanced odor‐mediated responses. Studies on the interaction of fetal and postnatal exposures using the social transmission paradigm have been limited to the responses of observers. When combined, the enhanced response is greater than either form of exposure alone and, in observer females, yields adult persistence. The absence of a male effect is noteworthy, given that chemosensory mechanisms are suggested to be an important antecedent factor in the progression of ethanol preference. Observers gain odor information on the breath of the demonstrator through social interaction. Demonstrators experience the pharmacologic properties of ethanol along with retronasal and hematogenic olfaction. Thus, we tested whether augmentation of the fetal ethanol‐induced behavioral response with postnatal exposure as a demonstrator differed from that as an observer. We also examined whether re‐exposure as a demonstrator yields persistence in both sexes. Methods: Pregnant dams were fed an ethanol containing or control liquid diet throughout gestation. Progeny received four ethanol or water exposures: one every 48 hours through either intragastric infusion or social interaction with the infused peer beginning on P29. The reflexive behavioral sniffing response to ethanol odor was tested at postnatal (P) day 37 or P90, using whole‐body plethysmography. Results: When tested in either adolescence or adulthood ‐ fetal ethanol exposed adolescent ethanol observers and demonstrators significantly differed in their odor‐mediated response to ethanol odor both between themselves and from their respective water controls. Nonetheless, adolescent ethanol re‐exposure as a demonstrator, like an observer, enhanced the reflexive sniffing response to ethanol odor at both testing ages by augmenting the known effects of prior fetal ethanol experience. At each age, the magnitude of the enhanced odor response in demonstrators was similar to that of observers. Interestingly, only re‐exposure as a demonstrator resulted in persistence of the behavioral response into adulthood in both sexes. Conclusions: The method of ethanol re‐exposure plays an important role in prolonging the odor‐mediated effects of fetal exposure. While ethanol odor‐specific exposure through social interaction is important, additional factors such as the pairing of retronasal and hematogenic olfaction with ethanol’s intoxicating properties appear necessary to achieve persistence in both sexes.
• 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. (Arch Otolaryngol Head Neck Surg. 1990;116:354-355)
Sweet flavorants enhance palatability and intake of alcohol in adolescent humans. We asked whether sweet flavorants have similar effects in adolescent rats. The inherent flavor of ethanol in adolescent rats is thought to consist of an aversive odor, bitter/sweet taste, and burning sensation. In Experiment 1, we compared ingestive responses of adolescent rats to 10% ethanol solutions with or without added flavorants using brief-access lick tests. We used 4 flavorants, which contained mixtures of saccharin and sucrose or saccharin, sucrose, and maltodextrin. The rats approached (and initiated licking from) the flavored ethanol solutions more quickly than they did unflavored ethanol, indicating that the flavorants attenuated the aversive odor of ethanol. The rats also licked at higher rates for the flavored than unflavored ethanol solutions, indicating that the flavorants increased the naso-oral acceptability of ethanol. In Experiment 2, we offered rats chow, water, and a flavored or unflavored ethanol solution every other day for 8 days. The rats consistently consumed substantially more of the flavored ethanol solutions than unflavored ethanol across the 8 days. When we switched the rats from the flavored to unflavored ethanol for 3 days, daily intake of ethanol plummeted. We conclude that sweet and sweet/maltodextrin flavorants promote high daily intake of ethanol in adolescent rats (i.e., 6-10 g/kg) and that they do so in large part by improving the naso-oral sensory attributes of ethanol.
Human fetal ethanol exposure is strongly associated with ethanol avidity during adolescence.Evidence that intrauterine olfactory experience influences chemosensory-guided postnatal behaviors suggests that an altered response to ethanol odor resulting from fetal exposure may contribute to later abuse risk.Using behavioral and neurophysiological methods, the authors tested whether ethanol exposure via the dam's diet resulted in an altered responsiveness to ethanol odor in infant and adult rats.Compared with controls, (a) fetal exposure tuned the neurophysiologic response of the olfactory epithelium to ethanol odor at some expense to its responsiveness to other odorants in infantile rats-this effect was absent in adults; (b) the neural effect in infantile rats was paralleled by an altered behavioral response to ethanol odor that was specific to this odorant-this effect was also absent in adults; and (c) a significant component of the infantile behavioral effect was attributable to ethanol's effect on the olfactory neural modality.These data provide evidence for an important relationship between prenatal ethanol experience and postnatal behavioral responsiveness to the drug that is modulated or determined by olfactory function.
