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Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference.

Previous findings demonstrate the involvement of the cholinergic NBM in the acquisition of the social transmission of food preference (STFP), a relational associative odor-guided learning task. There is also evidence that muscarinic receptors in the medial prefrontal cortex, an important NBM target area, may modulate olfactory associative memory. The present experiment determined the consequences of blocking muscarinic cholinergic receptors in a component of the medial prefrontal region (the prelimbic cortex) on the STFP task. Adult male Wistar rats were bilaterally infused with scopolamine (20 microg/site) prior to training and showed a severe impairment in the expression of the task measured in two retention sessions, both immediately and 24h after training. Local scopolamine injections in the prelimbic cortex did not affect other behavioral measures such as olfactory perception, social interaction, motivation to eat, neophobia, or exploration. Results suggest that muscarinic transmission in the prelimbic cortex is essential for the STFP, supporting the hypothesis that ACh in a specific prefrontal area is important for this naturalistic form of olfactory relational memory. Current data are discussed in the context of disruption of learning as a result of interferences in PLC functions such as behavioral flexibility, attention, and strategic planning.

Analysis of Variance↗

The effects of aging on the human sense of smell and its relationship to food choice.

Olfaction plays a significant role in the perception of foods. For the most part, taste is limited to sweet, sour, bitter, and salty. The sensory experiences during consumption of complex foods and drinks cannot be constructed from these units. Indeed, much of the taste of a meal derives from olfactory stimulation. Hence, factors that influence olfactory perception should affect treatment of food-related odors. This article initially reviews previously published observations on the effects of age on olfaction and food preferences and then presents the results of original analyses of data derived from a substantial database formed as a result of the National Geographic Smell Survey. Included in the Survey form were topics relevant to the present article. They include the following question: Would you eat something that smelled like this? Two of the odors in the Survey were food related and two were fragrance related. Hence, in addition, we assessed responses to the following question: Would you apply something that smelled like this to your body? Answers were affected in part by the age and gender of the respondent and by the perceived pleasantness and intensity of the odor.

Aging↗

Olfactory capacities in aging and Alzheimer's disease. Psychophysical and anatomic considerations.

Age-related alterations in the ability to smell are well documented. For example, more than three-fourths of individuals over the age of 80 have major difficulty detecting and identifying odors. Furthermore, olfactory dysfunction is among the first signs of Alzheimer's disease (AD). Indeed, the olfactory pathways of patients with AD evidence disproportionate numbers of neuritic plaques and neurofibrillary tangles relative to other sensory pathways, suggesting that the olfactory system may be the site of first involvement of the AD process. In this article, the literature related to age- and AD-related alterations in olfactory perception has been briefly reviewed, and several current hypotheses regarding the physiologic basis for these changes discussed.

Aged↗

Visualizing odor detection in olfactory cilia by calcium imaging.

To visualize odor detection in individual cilia of olfactory sensory neurons we have developed a new approach by using high-resolution calcium imaging techniques. Laser scanning confocal microscopy revealed, for the first time, that odor stimuli induce transient Ca2+ elevations in single olfactory cilia. Pharmacological analysis indicates that these Ca2+ signals depend entirely on Ca2+ entry through activated cyclic nucleotide-gated (CNG) channels. This novel approach enables us to monitor the initial steps leading to olfactory perception in a spatially and temporally resolved manner.

Animals↗

Environment and medication use influence olfactory abilities of older adults.

BACKGROUND: Age-associated changes in eating behavior and nutritional status are often caused by changes in olfactory perception. OBJECTIVE: This study determined the relative contribution of medication use and environmental risk to age-associated change in olfaction. DESIGN: Fifty participants aged 50-96 (M = 70.4) in two groups (environmentally at-risk and low-risk) were administered a set of four olfactory tasks, WAIS Vocabulary, MMSE, and demographic questionnaires. Environmental risk was defined as having worked in places where exposure to caustic fumes (e.g., formaldehyde, toluene, etc.) was common and long-term. Olfactory tasks included detection thresholds for phenethyl alcohol (PEA; assesses olfactory function) and menthol (assesses olfactory and trigeminal function); odor recognition in a forced-choice paradigm; odor difference discrimination; and odor identification with supplied names. RESULTS: The high-risk group had significantly higher thresholds for PEA, and significant within-group variability for menthol. Medication usage and cognitive status were significantly associated with odor recognition. Only medication was strongly associated with the odor discrimination task. Medication usage, environmental risk, and age in order were found to be the greatest risk factors for odor identification. CONCLUSION: These results highlight the need to carefully consider environmental and pharmacological effects in age-associated sensory tasks.

Aged↗

Changes in the olfactory mucosa of the black bullhead Ictalurus melas induced by exposure to sublethal concentrations of sodium dodecylbenzene sulphonate.

The effects of exposure to sublethal concentrations (1.5 and 3 mg l(-1)) of sodium dodecylbenzene sulphonate on the olfactory epithelium of Ictalurus melas Rafinesque were examined by light and scanning electron microscopy. The detergent affected the superficial part of each olfactory lamella and different morphological alterations, depending on dose and duration of treatment, were observed. The histology and surface morphology of sensory and non-sensory areas of the epithelium of fish treated with 1.5 mg l(-1) for 5 and 10 d were not affected by the treatment, while only an incipient thinning-out of the long cilia of non-sensory epithelium was seen in fish treated for 15 d. Treatment with 3 mg l(-1) caused morphological alterations, related to the time of exposure, in the non-sensory and sensory epithelium, consisting of progressive thinning of cellular projections; this treatment also increased mucus production. These observed histopathological changes in the olfactory mucosa may modify the olfactory perception of the fish, and could thereby impair important physiological functions such as feeding, social interactions or migration.

Animals↗

The effect of temperature, humidity and peak inspiratory nasal flow on olfactory thresholds.

Temperature, humidity and nasal peak inspiratory flow rate (PIFR) are potential variables in the quantitative measurement of olfactory thresholds in the clinic. To date, these variables have not been properly evaluated with respect to olfactory perception, and therefore the aim of this study was to determine their effect on the thresholds. These variables were measured on 10 occasions in 10 subjects over a 10-week period. The results obtained were then subjected to statistical analysis using a linear mixed-effect model. This demonstrated that olfactory thresholds are sufficiently independent of room temperature, peak humidity and nasal PIFR in a routine outpatient clinic environment in normal subjects, with no evidence of any statistically significant influence by these variables.

Adult↗

[Evaluation of olfactory stimuli by depressed patients].

Anhedonia, a cardinal sign of depression, is discussed to originate from a transmitter dysbalance in the central dopaminergic reward system. This system involves neuroanatomically many structures of the olfactory system. Hence the question arises whether anhedonia can be quantified when depressive patients judge smells hedonically. Sensory evaluation of olfactory stimuli by 16 depressive patients was compared that of an age-matched control group. In the group comparison, mono- and birhinal sensory thresholds as well as judgment of intensity were not significantly different. For four of the eight smells, the hedonic judgements were found to be identical between the group of depressives and controls, with the remaining smells not significantly different. There were no differences in the consistency of ranking of smells. In a longitudinal (test-retest) assessment there were again no differences in intensity, familiarity, and hedonic quality of the smells. The findings suggest that changes in the dopaminergic transmitter balance during the state of depression causing anhedonia affect neither olfactory perception nor the hedonic judgement of smells. Contrary to the clinical picture, anhedonia thus seems not to arise at the level of sensory perception yet but should be considered a more complex construct of disturbed central processing.

Adult↗

Modulation by cGMP of the voltage-gated currents in newt olfactory receptor cells.

Effects of cGMP on voltage-gated currents in the somatic membrane of isolated newt olfactory receptor cells were investigated using the whole-cell mode of the patch-clamp technique. Under voltage clamp, membrane depolarization generated time- and voltage-dependent current responses, a transient inward current and a sustained outward current. When cGMP or a membrane permeant analog of cGMP, 8-p-chlorophenylthio-cGMP (CPT-cGMP), was applied to the recorded cell, the amplitude of the transient inward current increased markedly, but that of the sustained outward current did not change significantly. When each current was isolated by pharmacological agents, 0.1 mM CPT-cGMP increased the peak amplitude of a Na(+) current (I(Na)) by approximately 40%, a T-type Ca(2+) current (I(Ca,T)) by approximately 40%, and an L-type Ca(2+)current (I(Ca,L)) by approximately 10%; however it did not change significantly the amplitude of a delayed rectifier K(+) current (I(K)). A selective cGMP-dependent protein kinase inhibitor, KT5823, blocked the enhancement by cGMP of I(Na) and I(Ca,T), suggesting that cGMP increases these currents via cGMP-dependent phosphorylation. Under current-clamp conditions, application of CPT-cGMP lowered the current threshold of action potentials induced by current injection, and increased the maximum spike frequency in response to strong stimuli. We suggest that cGMP may lower the threshold in olfactory perception by decreasing the current threshold to generate spikes, and also prevent the saturation of odor signals by increasing the maximum spike frequency.

Action Potentials↗

Identification of latent variables in a semantic odor profile database using principal component analysis.

Many classifications of odors have been proposed, but none of them have yet gained wide acceptance. Odor sensation is usually described by means of odor character descriptors. If these semantic profiles are obtained for a large diversity of compounds, the resulting database can be considered representative of odor perception space. Few of these comprehensive databases are publicly available, being a valuable source of information for fragrance research. Their statistical analysis has revealed that the underlying structure of odor space is high dimensional and not governed by a few primary odors. In a new effort to study the underlying sensory dimensions of the multivariate olfactory perception space, we have applied principal component analysis to a database of 881 perfume materials with semantic profiles comprising 82 odor descriptors. The relationships identified between the descriptors are consistent with those reported in similar studies and have allowed their classification into 17 odor classes.

Cluster Analysis↗

Plasticity in the olfactory system: lessons for the neurobiology of memory.

We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory.

Animals↗

Olfactory information processing during the course of the menstrual cycle.

In the present study we examined whether olfactory information processing depends on the phase of the menstrual cycle. Five female subjects were investigated during three phases (follicular, ovulatory, luteal) of their menstrual cycle. In each session chemosensory (olfactory) event-related potentials (CSERP) were recorded and olfactory thresholds and the hedonic tone of the test stimulus (citral) were determined. Threshold values were correlated with the salivary cortisol level. The results show that olfactory perception changes during the menstrual cycle. After the first stimulus presentations in a recording session, odors were perceived as more complex or novel during the ovulatory period (enhanced amplitude of P3-1). With continued stimulation, odor processing became faster (reduced latency of NI, P2 and P3-2) around ovulation and slower during the follicular phase. Moreover, odors were described more differentially during the ovulatory period. Olfactory sensitivity was correlated positively with the peripheral cortisol level.

Adult↗

Comparative analysis of olfactory receptor repertoires reveals evolutionary dynamics and high-altitude adaptation in Schizopygopsis younghusbandi based on the chromosome-level genomes.

The olfactory receptor (OR) gene represent a significant multigene family in vertebrates, forming the core molecular basis of olfactory perception and playing a crucial role in the environmental adaptation of species. High-altitude ecosystems represent extreme habitats characterized by specific abiotic stresses, including low oxygen levels, low temperatures, and intense ultraviolet radiation. These environments also exhibit low aquatic biodiversity and a limited variety of odor molecules, factors that have influenced the adaptive evolution of the sensory systems in endemic species. However, the genetic mechanisms underlying olfactory adaptation in high-altitude freshwater fish remained inadequately understood. In this study, we performed comparative genomics analyses to reveal the evolutionary processes underlying the adaptive and functional evolution of OR genes in S. younghusbandi, a cyprinid fish endemic to the Qinghai-Xizang Plateau. The results indicated that, compared to their low-altitude relatives, S. younghusbandi possessed a significantly smaller number of OR genes, with only 98 genes, which revealed the contraction of the gene family. Phylogenetic analysis revealed that the OR genes of cyprinid fish could be categorized into two major lineages: type I and type II. The η and δ families, which perceive water-soluble odors, in S. younghusbandi underwent significant and specific expansion, while the ε family was completely absent. This pattern reflected adaptive changes in olfactory recognition to accommodate the simplified odor spectrum of high-altitude water bodies. Chromosomal localization analysis demonstrated that OR genes were clustered, and collinearity analysis confirmed the presence of conserved genomic fragments among species. Selection pressure analysis revealed that the Ka/Ks values of all homologous gene pairs were less than 1, indicating that the OR genes of S. younghusbandi underwent strong purifying selection as a group to preserve core olfactory function. A few genes exhibited relaxed selection characteristics, which may have facilitated the fine-tuning of adaptability to high-altitude environments. In conclusion, this study elucidated the evolutionary dynamics and adaptive characteristics of the OR gene in S. younghusbandi, offering a new perspective on the molecular mechanisms underlying olfactory adaptation at high altitudes and enriching the research on sensory evolution in vertebrates.

Schizopygopsis younghusbandi↗

Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase.

Xenobiotic metabolizing enzymes in the olfactory epithelium have been suggested to catalyse inactivation and facilitate elimination of odorants. We report here the molecular cloning and functional characterization of a human olfactory UDP-glucuronosyltransferase (UGT). The cloned protein is composed of 527 amino acids with an identity of 87% with a rat olfactory UGT and of 43-62% with other human UGT isoforms. Based on the sequence homology, it has been designated hUGT2A1. The gene was mapped to chromosome 4q13 by fluorescence in situ hybridization. The expression appeared to be specific for the olfactory tissue. The substrate specificity of this isoform was assessed using Chinese hamster V79 cells stably transfected with the isolated cDNA. The expressed enzyme showed a broad substrate spectrum including a range of phenolic compounds as well as aliphatic and monoterpenoid alcohols, among them many odorants. Furthermore, some steroids, especially androgens, some drugs and carcinogens were conjugated. The results support a role of the enzyme in olfactory perception and in protection of the neural system against airborne hazardous chemicals.

Alcohols↗

Inspiratory phase-locked alpha oscillation in human olfaction: source generators estimated by a dipole tracing method.

Olfactory perception and related emotions are largely dependent on inspiration. We acquired simultaneous respiration and electroencephalographic recordings during pleasant odour and unpleasant odour stimulation. We sought to identify changes in respiratory pattern, inspiratory-related potentials and location of dipoles estimated from the potentials. Electroencephalographic recording was triggered by inspiration onset. Respiratory frequency decreased at pleasant odour recognition, and it increased at unpleasant odour detection and recognition. O2 consumption records showed that these changes were not due to metabolic demand. During olfactory stimulation, inspiratory phase-locked alpha oscillation (I-alpha) was found in the averaged potential triggered by inspiration onset. I-alpha was observed at both pleasant odour and unpleasant odour detection and recognition, but it was not seen in the inspiration-triggered potentials of normal air breathing. Electroencephalographic dipole tracing identified the location of dipoles from the I-alpha in the limbic area and the cortex; the entorhinal cortex, hippocampus, amygdala, premotor area and centroposterior orbitofrontal cortex subserve odour detection, and the rostromedial orbitofrontal cortex subserves odour recognition. We suggest that the I-alpha in our study originated from the olfactory cortex in the forebrain and was phase-locked to inspiration.

Action Potentials↗

[Sex differences in memory performance for odors, tone sequences and colors].

Sense of olfaction would seem to be of little importance for human behavior. However, a closer look at this from the psychological point of view reveals many interesting aspects, such as sex differences in olfactory perception, that are of interest to differential psychology. The present study deals with sex differences in the memory for odors; we assume that women will do better here than men while other memory tasks involving acoustical and optical stimuli will show no such differences. Sixty women and 40 men were examined. On the first day, they had to retain 10 odors, 10 random-generated tone-sequences, and 10 colors. On the second day, 20 such stimuli for each memory task were presented, and the subjects had to remember and to tell which were known and which of them were unknown stimuli to them. A significant advantage in the olfaction memory task was found for women, while acoustical and optical memory scores showed no such differences. This expected finding is discussed in two ways. First, the female advantage might result from phylogenetic sources. Second, it might arise because women in general more often than men seem to deal with olfactory cues, so that they might simply have more experience and therefore the greater chance to score higher in an odor memory task.

Adult↗

Dorsal hippocampal contributions to unimodal contextual conditioning.

Although there is general consensus that the hippocampus is not critically involved in the acquisition of fear conditioned to an explicit conditioned stimulus (CS), the extent to which the hippocampus participates in contextual fear conditioning remains unclear. To further characterize the potential role of the hippocampus in contextual fear conditioning, the present experiments examined the effect of excitotoxic lesions of dorsal hippocampus on the acquisition of a novel contextual fear conditioning paradigm in which a unimodal (olfactory) cue served to disambiguate discrete "contexts" within a single behavioral training chamber. Selective lesions of dorsal hippocampus severely attenuated olfactory contextual conditioning without affecting conditioning to an explicit auditory or olfactory CS. Additional experiments indicate that these contextual conditioning deficits cannot be attributed to a lesion-induced decrement in olfactory perception, a preferential impairment of "weak" forms of conditioning, or hyperactivity. Thus, the hippocampus appears to contribute importantly to the acquisition of fear conditioned to explicitly nonspatial, unimodal, temporally, and spatially diffuse contextual stimuli.

Acoustic Stimulation↗

Olfactory event-related potentials in psychosis-prone subjects.

Previous studies in schizophrenic patients have suggested that there are changes in olfactory sensitivity. In order to externally validate a psychometrical assessment of the psychosis-risk indicated by schizotypic factors, this study was carried out to determine whether changes in olfactory perception could be determined even for persons merely at risk of developing schizophrenia. These 'psychosis-prone' subjects consistently scored high in either the scale for 'physical anhedonia' (PA) or the scale for 'perceptual aberration' (PAB). Thus, three groups were investigated (control, n = 11; PA, n = 12; PAB, n = 12). Each subject participated in one testing session where the two odorants, vanillin (pleasant) and hydrogen sulphide (unpleasant), were applied by means of a specially designed delivery apparatus. Subjects rated both the intensity and the hedonic quality of the stimuli. In addition, olfactory event-related potentials (OERP) were recorded after dichotomous stimulation. In general, there were only few significant differences between the three groups investigated. Contrary to expectations, ratings for pleasantness of vanillin were highest in PA subjects compared to PAB subjects and controls (p < 0.05). Correspondingly, OERP amplitudes in response to vanillin were largest within the PA group (p < 0.05). For hydrogen sulphide, PAB subjects showed the smallest OERP amplitudes (p < 0.05). In addition, it was observed that female subjects had significantly larger OERP amplitudes when compared to male subjects (p < 0.05), which possibly indicates gender differences in olfactory sensitivity.

Adult↗