bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Functional Changes in Rats Administered with Monosodium l‐Glutamate in the Stomach
Authors: Kondoh Takashi , Tsurugizawa Tomokazu , Torii Kunio
Published: July 2009

Recent studies have demonstrated the existence of receptors for l‐glutamate (GLU) and their transduction molecules in the gut mucosa as well as in the oral cavity. Among 20 amino acids, gastric vagal afferent fibers respond only to intragastric administration of GLU. Functional magnetic resonance imaging revealed activation of several forebrain regions in response to intragastric infusion of taste solutions (d‐glucose [sweet], monosodium l‐glutamate [MSG; umami], and NaCl [salty] at 60 mM) in rats. Glucose activated the nucleus accumbens. MSG activated the medial preoptic area, dorsomedial nucleus of the hypothalamus, and habenular nucleus. Both glucose and MSG activated the amygdala. Some areas, such as the insular cortex, anterior cingulate cortex, hippocampus, and caudate–putamen were activated by all three substances. Glucose‐induced brain activation developed slowly and persisted for a long time, whereas activation by MSG developed rapidly during infusion and reduced rapidly after cessation of infusion. NaCl induced only small and transient activation. Thus, both activated areas and temporal response patterns in the brain were distinct between sweet and umami substances delivered in the stomach. Postoral taste substances may activate the brain via neural (vagal) and/or humoral pathways.
Individual Odor Recognition in Procellariiform Chicks
Authors: O’Dwyer Terence W. , Nevitt Gabrielle A.
Published: July 2009

Since the groundbreaking work of Wenzel, Bang, and Grubb in the 1960s, enormous progress has been made toward elucidating the sense of smell in procellariiform seabirds. Although it is now well established that adult procellariiforms use olfaction in many behaviors, such as for foraging, nest relocation, and mate recognition, the olfactory abilities of petrel chicks are less well understood. Recent studies have shown that petrel chicks can recognize prey‐related odors and odors associated with their nest before leaving their burrow for the first time. The recognition of burrow odors by petrel chicks is unlikely to be used for homing, and we have suggested that chicks may be learning personal odors associated with the nest's occupants for use later in life in the context of kin recognition or mate choice. The source of personal odors in petrels is unknown. However, in other vertebrates, the major histocompatibility complex influences body odors, which in turn influence mating preferences. It is not currently known whether this highly polymorphic gene region influences body odors and individual recognition in the procellariiforms, but this could be a fruitful area of future research.
Trafficking of Mammalian Chemosensory Receptors by Receptor‐transporting Proteins
Authors: Matsunami Hiroaki , Mainland Joel D. , Dey Sandeepa
Published: July 2009

Although mammalian odorant receptors (ORs) were identified more than 15 years ago, we still do not understand how odorant molecules interact with ORs at a molecular level. Previous studies of mammalian ORs have tested few ORs against many odorants. Some fundamental properties of the olfactory system, however, require investigation of a wide panel of diverse ORs with many chemically diverse odorants. Previously, we identified OR accessory proteins, receptor‐transporting protein (RTP) 1 and RTP2. They are expressed specifically in olfactory neurons, are associated with OR proteins, and facilitate the OR trafficking to the plasma membrane when coexpressed in mammalian cell lines. With this approach, high‐throughput screening using a large repertoire of mammalian ORs is now possible. The activation profiles can be used to develop a predictive model relating physicochemical odorant properties, receptor sequences, and their interactions, enabling us to predict a tested receptor's response to a novel odorant and a novel receptor's response to a tested odorant. Doing so will provide a basis for understanding how structurally diverse odorant molecules activate the mammalian OR repertoire. Similarly, two families of vomeronasal receptors, V1Rs and V2Rs, are also notoriously difficult to functionally express in heterologous cells. However, coexpression of the RTP family members with V1Rs or V2Rs does not seem to facilitate trafficking of the receptor proteins. This finding suggests that the vomeronasal organ has a unique biosynthetic pathway for membrane proteins.
Modulation and Transmission of Sweet Taste Information for Energy Homeostasis
Authors: Sanematsu Keisuke , Horio Nao , Murata Yoshihiro , Yoshida Ryusuke , Ohkuri Tadahiro , Shigemura Noriatsu , Ninomiya Yuzo
Published: July 2009

Perception of sweet taste is important for animals to detect external energy source of calories. In mice, sweet‐sensitive cells possess a leptin receptor. Increase of plasma leptin with increasing internal energy storage in the adipose tissue suppresses sweet taste responses via this receptor. Data from our recent studies indicate that leptin may also modulate sweet taste sensation in humans with a diurnal variation in sweet sensitivity. This leptin modulation of sweet taste information to the brain may influence individuals’ preference and ingestive behavior, thereby playing important roles in regulation of energy homeostasis.
Bitter Taste Receptors and Their Cells
Authors: Behrens Maik , Reichling Claudia , Batram Claudia , Brockhoff Anne , Meyerhof Wolfgang
Published: July 2009

The molecular basis of human bitter taste perception is an area of intense research. Only 25 G protein‐coupled receptors belonging to the hTAS2R gene family face the challenge to detect thousands of structurally different bitter compounds, most of which are plant metabolites. Since many natural bitter compounds are highly toxic, whereas others are part of our daily diets, bitter taste was crucial during evolution and still most likely affects our food selection. The article presented here addresses biosynthesis, functional analyses of TAS2Rs and TAS2R variants, as well as gustatory expression of hTAS2R genes.
Toward Identifying Sex Pheromones in Blue Crabs
Authors: Kamio Michiya
Published: July 2009

Experimental approaches to identify sex pheromones of blue crabs are outlined. I describe how consideration of the ecological context of mating behavior can lead to the development of more reliable bioassays. I also describe chemical analyses that demonstrate differences in the chemical composition of urines from animals of different sex and maturity, which indicates the promise of using biomarker targeting in identifying sex pheromones.
Information Processing in the Parabrachial Nucleus of the Pons
Authors: Di Lorenzo Patricia M. , Platt Daniel , Victor Jonathan D.
Published: July 2009

As the second synapse in the central gustatory pathway of the rodent, the parabrachial nucleus of the pons (PbN) receives information about taste stimuli directly from the nucleus of the solitary tract (NTS). Data show that NTS cells amplify taste responses before transmitting taste‐related signals to the PbN. NTS cells of varied response profiles send converging input to PbN cells, though input from NTS cells with similar profiles is more effective at driving PbN responses. PbN cells follow NTS input for the first 3 s of taste stimulation for NaCl, HCl, and quinine, but are driven in cyclic bursts throughout the response interval for sucrose. Analyses of the temporal characteristics of NTS and PbN responses show that both structures use temporal coding with equal effectiveness to identify taste quality. Thus, the NTS input to the PbN is comprehensive, in that PbN cells receive NTS input that could support broad sensitivity, systematic, in that the time course of PbN firing patterns depend reliably on the tastant, and efficient, in that information from the NTS is preserved as it is communicated across structures. Comparisons of NTS and PbN taste responses in rats form the basis for our speculation that in primates, where the central gustatory pathway does not synapse in the PbN, the function of the PbN in taste processing may have been incorporated into that of the NTS.
Electrophysiology of Vagal Afferents
Authors: Horn Charles C.
Published: July 2009

The alimentary canal includes the mouth, stomach, and intestines, and is connected to the brain by thousands of chemosensory neurons. In contrast to the understanding of the lingual taste system, there is little insight into the chemosensory function of other regions of the alimentary canal. The presence of known taste receptors in the gastrointestinal tract suggests a similarity to taste mechanisms present in the oral cavity. Afferent fibers of the vagus play a prominent role in signaling the chemical contents of the gastrointestinal tract to the hindbrain and this information can be used to elicit defensive responses, such as vomiting or nutritional responses. A host of amino acids are likely detected by vagal afferent fibers, but the initial sensory transduction of these stimuli and functional significance remains a mystery. Several problems with recording the electrophysiological signals of vagal afferents are discussed, with particular reference to sampling the afferent signals from the duodenum and liver region.
Drosophila sechellia as a Model in Chemosensory Neuroecology
Authors: Stensmyr Marcus C.
Published: July 2009

The olfactory system directly interfaces with the environment, and thus changes in the environment or an animal's habits would presumably also lead to changes in the olfactory system. Comparative studies on specialized animals with known generalist ancestors could hence be a way of revealing general processes shaping olfactory systems as well as highlighting the importance and function of specific chemosensory genes. Drosophila sechellia, a close relative of D. melanogaster, and highly specialized towards the use of the toxic Morinda fruit, has been the subject of several studies aimed at pinpointing the consequences of host choice to the chemosensory system, from the molecular level to behavior. This paper highlights some recent (and not so recent) advances in this area and concludes with a brief discussion on the antiquity of the D. sechellia–Morinda connection.
Centrifugal Drive onto Local Inhibitory Interneurons of the Olfactory Bulb
Authors: Mouret Aurélie , Murray Kerren , Lledo Pierre‐Marie
Published: July 2009

The olfactory bulb is known to receive signals from sensory neurons and to convey them to higher processing centers. However, in addition to relaying sensory information to the cortex, the olfactory bulb is actively involved in sensory information processing. Hence, olfactory sensory inputs generate a reproducible spatial pattern of restricted activation in the glomerular layer that is subsequently transformed into highly distributed patterns by lateral interactions between output relay neurons and diverse types of local interneurons. Odor representation is thus highly dynamic and temporally orchestrated, right from the first central relay of the olfactory system. This major function of the olfactory bulb is subject to extensive local and extrinsic synaptic influences. The external (or centrifugal) inputs include the dense innervations preferentially targeting the granule cells of the olfactory bulb. The continuous arrival of newly generated neurons in the olfactory bulb of adults provides another source of plasticity influencing the olfactory circuitry. This review deals with the neuromodulation of granule cell activity and of the continuous recruitment of these cells throughout life.
Identification of the Key Bitter Compounds in Our Daily Diet Is a Prerequisite for the Understanding of the hTAS2R Gene Polymorphisms Affecting Food Choice
Authors: Hofmann Thomas
Published: July 2009

In order to decode genetic variations affecting food choice and to determine whether to accept or to reject certain food products, it is a necessary prerequisite to deorphanize the hTAS2R/ligand pairs using the key bitter compounds in foods as stimuli rather than doing this either by using artificial molcules, to which the normal consumer had never been exposed, or by using food‐born molecules which do not at all contribute to the overall bitterness. Therefore, the chemical structure of the most active bitter molecules in foods needs to be unequivocally determined in order to be sure that hTAS2R polymorphisms are related to the key molecules which really contribute to the overall bitterness perception of food products. As most studies focused primarily on quantitatively predominating compounds, rather than selecting the target compounds to be identified with regard to taste‐activity, it seems that yet unknown components play a key role in evoking the bitter taste of food products. Driven by the need to discover the key players inducing the food taste, the research area “sensomics” made tremendous efforts in recent years to map the sensometabolome and to identify the most intense taste‐active metabolites in fresh and processed foods. The present article summarizes recent studies on the identification of orphan key bitter stimuli in fresh, fermented, and thermally processed foods using carrots, cheese, and roasted coffee as examples.
Genetic Variation in Taste Sensitivity to 6‐n‐Propylthiouracil and Its Relationship to Taste Perception and Food Selection
Authors: Tepper Beverly J. , White Elizabeth A. , Koelliker Yvonne , Lanzara Carmela , D'Adamo Pio , Gasparini Paolo
Published: July 2009

The ability to taste bitter thiourea compounds and related chemicals is a well‐known human trait. The majority of individuals perceive these compounds, typified by the bitterness of 6‐n‐propylthiouracil (PROP) and phenylthiocarbamide (PTC), as moderately‐to‐extremely bitter. Approximately 30% of the population is taste blind to these substances. It has been hypothesized that PROP/PTC tasters are more sensitive to other bitter tastes, sweet taste, the pungency of chili peppers, the astringency of alcohol, and the texture of fats. Tasters may also show lower preferences for foods with these taste qualities than nontasters who show the opposite set of responses (i.e., lower taste sensitivities and higher preferences for these sensory qualities). This pathway is illustrated in the following model:
image

Robust associations between PROP status and taste perceptions have been well documented. However, subsequent links to food preferences and diet selection have been more difficult to demonstrate. This is not surprising given the complexity of human ingestive behavior that is influenced by numerous factors including health attitudes, personality traits, and cultural norms. Our laboratory has been using PROP screening to investigate individual differences in the selection of bitter foods, especially bitter tasting vegetables and fruits that may have long‐term health implications. This chapter will discuss new and recent findings addressing the following issues: 1) whether PROP‐related differences in perception of bitter compounds predict the perception and liking of bitter foods; 2) the role of bitter taste modifiers; and 3) the influence of personal characteristics such as food attitudes and cultural background on PROP‐related food preferences.
Evaluating the Prevalence of Olfactory Dysfunction in a Pediatric Population
Authors: Dalton Pamela , Mennella Julie A. , Cowart Beverly J. , Maute Christopher , Pribitkin Edmund A. , Reilly James S.
Published: July 2009

Although smell loss has several potential etiologies (e.g., head trauma, allergic rhinitis, and enlarged adenoids) that are common among children, studies evaluating the prevalence of olfactory dysfunction in the pediatric population are rare. Several challenges confront the clinician or researcher hoping to evaluate odor identification ability in young children. Children are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select from alternative choices, which is the typical adult response option. Consequently, specialized forms of olfactory tests must be developed for this population. Based on the format of the San Diego Odor Identification Test1 and the delivery system of the Brief Smell Identification Test,2 we are developing a short form odor identification test utilizing standardized odor stimuli in which participants match 6 odorants to pictures of the odor source. The pilot version of this test is being administered to children between the ages of 3–17 as part of the pre‐surgical intake evaluation at the A.I. duPont Hospital for Children and as part of basic research studies at the Monell Center. The hospital study population is broad and includes children undergoing ear, nose, and throat surgery as well as controls subjects (children undergoing general surgery), with approximately 50 children per week eligible for evaluation. To improve correct interpretation of the results, stimulus familiarity is evaluated by having the child's parent/guardian also complete the test and answer a short questionnaire about the child's experience with the various odor stimuli. The challenges confronted in studying this clinical population as well as extrapolation to larger populations will be discussed.
Behavioral Modulation of Gustatory Cortical Activity
Authors: Fontanini Alfredo , Katz Donald B.
Published: July 2009

Our perception of the sensory world is constantly modulated by the environment surrounding us and by our psychological state; each encounter with the same stimulus can in fact evoke very different perceptions. This phenomenological richness correlates well with the plasticity and the state‐dependency observed in neural responses to sensory stimuli. This article reviews recent results on how the processing of sensory inputs varies depending on the internal state of the animal. Specifically it focuses on the gustatory system and on data showing that levels of attention and expectation modulate taste processing and gustatory cortical activity in meaningful ways. Mounting experimental evidence suggesting that expectation‐dependent changes in gustatory cortical activity result from changes in the coupling between the amygdala and the cortex will also be discussed. The results presented here begin to paint a complex picture of taste, which goes beyond the framework of classical coding theories.
Effects of Aging on the Human Taste System
Authors: Schiffman Susan S.
Published: July 2009

Losses in taste perception as well as distortions of gustatory function occur with greater frequency in older individuals, and these changes are exacerbated by certain medical conditions, pharmacologic interventions, radiation, and exposure to toxic chemicals. Medications, especially drug–drug interactions, are the most significant yet underappreciated contributors to taste disorders in the elderly. Taste disorders frequently occur when the fraction of an orally administered drug dose that reaches the systemic circulation is markedly increased due to inhibition (by a coadministered drug) of the efflux transporter P‐glycoprotein and/or inhibition of the cytochrome P450 metabolism system, which normally limit systemic availability of drugs. The supratherapeutic plasma drug concentrations that result from drug–drug interactions can induce a taste from the blood side of taste cells (intravascular taste), alter taste cell biochemistry, and/or modify other aspects of the taste pathways.
desat1 and the Evolution of Pheromonal Communication in Drosophila
Authors: Bousquet François , Houot Benjamin , Chauvel Isabelle , Dupas Stéphane , Ferveur Jean‐François
Published: July 2009

The evolution of communication is a fundamental biological problem. The genetic control of the signal and its reception must be tightly coadapted, especially in interindividual sexual communication. However, there is very little experimental evidence for tight genetic linkage connecting the emission of a signal and its reception. In Drosophila melanogaster, desat1 is the first known gene that simultaneously affects the emission and the perception of sex pheromones. Our experiments show that both aspects of pheromonal communication (the emission and the perception of sex pheromones) depend on distinct genetic control and may result from tissue‐specific expression of different transcripts, all coding for the same desaturase. Therefore, and given the high conservation of its coding region, the pleiotropic activity of the desat1 gene may have arisen from an evolutionary process that shaped its regulatory regions.
Qualitative Effects in Nasal Trigeminal Chemoreception
Authors: Shusterman Dennis
Published: July 2009

Olfaction and nasal trigeminal chemoreception together convey an impression of the physical and chemical qualities of inspired air. “Nasal pungency” refers to the nasal trigeminal impact of inhaled air pollutants as well as spicy foods and selected medicaments. Such diverse sensations as cooling, numbness, tingling, itching, burning, and stinging are all conveyed by the trigeminal system yet are successfully differentiated in psychophysical testing, with or without concomitant olfactory information. Here we briefly review the neurobiological and psychophysical evidence for qualitative specificity in the nasal trigeminal system.
Age‐related Changes in Associative Learning for Olfactory and Visual Stimuli in Rodents
Authors: Gilbert Paul E. , Pirogovsky Eva , Brushfield Andrea M. , Luu Trinh T. , Tolentino Jerlyn C. , Renteria Adam F.
Published: July 2009

Memory for olfactory stimuli may be particularly affected by age‐related brain changes in humans and may be an early indicator of cognitive impairment and Alzheimer's disease. Studies involving rats have offered insights into impaired cognition in aged animals, but few have examined odor memory. Therefore, it is unclear whether aged rats are a good model for possible age‐related changes in odor memory in humans. Young (6‐month‐old) and old (24‐month‐old) rats were tested on associative learning tasks involving visual and olfactory stimuli. The first task examined age‐related differences in discrimination and reversal learning for olfactory and visual stimuli; the second task utilized an associative contextual learning task involving olfactory and visual cues. Although old rats were able to perform the olfactory and visual discrimination tasks as well as young rats, old rats displayed significant age‐related impairment on the reversal learning and contextual learning tasks. The results suggest that aging may have a similar deleterious effect on odor memory in rats and in humans. The findings may have important implications for the selection of memory paradigms for future research studies on aging. In addition, the use of an animal model to investigate the effects of aging on odor memory will allow researchers the ability to investigate how age‐related neuroanatomical and neurochemical changes may result in impaired odor memory.
Processing of Odor Representations by Neuronal Circuits in the Olfactory Bulb
Authors: Friedrich Rainer W. , Yaksi Emre , Judkewitz Benjamin , Wiechert Martin T.
Published: July 2009

In order to analyze neuronal computations in the first olfactory processing center, the olfactory bulb, we measured odor‐evoked activity patterns across large numbers of neurons within the intact olfactory bulb of zebrafish using optical and electrophysiological methods. We found that the olfactory bulb performs multiple computations including a decorrelation of overlapping inputs, a multiplexing of complementary information, and gain control. Patterns of olfactory bulb output activity are reorganized during the initial phase of an odor response, resulting in a partial loss of the topographic representation of molecular features and in the decorrelation of activity patterns evoked by similar stimuli. Physiological, pharmacological, and computational results provide initial insights into the mechanisms underlying these computations.
Olfactory Memory
Authors: Eichenbaum Howard , Robitsek R. Jonathan
Published: July 2009

Odor‐recognition memory in rodents may provide a valuable model of cognitive aging. In a recent study we used signal detection analyses to distinguish odor recognition based on recollection versus that based on familiarity. Aged rats were selectively impaired in recollection, with relative sparing of familiarity, and the deficits in recollection were correlated with spatial memory impairments. These results complement electrophysiological findings indicating age‐associated deficits in the ability of hippocampal neurons to differentiate contextual information, and this information‐processing impairment may underlie the common age‐associated decline in olfactory and spatial memory.
Olfactory Impairment in Presymptomatic Alzheimer's Disease
Authors: Wilson Robert S. , Arnold Steven E. , Schneider Julie A. , Boyle Patricia A. , Buchman Aron S. , Bennett David A.
Published: July 2009

Alzheimer's disease (AD) impairs olfaction, but it is uncertain how early this occurs in the disease process and whether the effect can be accounted for by other behavioral or genetic markers of the disease. We administered the Brief Smell Identification Test (BSIT) to 471 older people without dementia or cognitive impairment who then completed annual clinical evaluations and brain autopsy at death. BSIT score was associated with more rapid decline in episodic memory and with increased risk of developing incident mild cognitive impairment (MCI), even after controlling for baseline level of episodic memory and possession of an apolipoprotein E ɛ4 allele. In 34 people who died without evidence of cognitive impairment, lower BSIT score was associated with higher level of AD pathology, even after controlling for ɛ4 and for level of episodic memory function when olfaction was assessed. These analyses suggest that among older people without clinical manifestations of AD or MCI, olfactory dysfunction is related to both the level of AD pathology in the brain and the risk of subsequently developing prodromal symptoms of the disease, and that these associations persist after accounting for the effects of other recognized behavioral and genetic markers of the disease.
Trace Amine‐associated Receptors Are Olfactory Receptors in Vertebrates
Authors: Liberles Stephen D.
Published: July 2009

The mammalian nose is a powerful chemosensor, capable of detecting and distinguishing a myriad of chemicals. Sensory neurons in the olfactory epithelium contain two types of chemosensory G protein‐coupled receptors (GPCRs): odorant receptors (ORs), which are encoded by the largest gene family in mammals, and trace amine‐associated receptors (TAARs), a smaller family of receptors distantly related to biogenic amine receptors. Do TAARs play a specialized role in olfaction distinct from that of ORs? Genes encoding TAARs are found in diverse vertebrates, from fish to mice to humans. Like OR genes, each Taar gene defines a unique population of canonical sensory neurons dispersed in a single zone of the olfactory epithelium. Ligands for mouse TAARs include a number of volatile amines, several of which are natural constituents of mouse urine, a rich source of rodent social cues. One chemical, 2‐phenylethylamine, is reported to be enriched in the urine of stressed animals, and two others, trimethylamine and isoamylamine, are enriched in male versus female urine. Furthermore, isoamylamine has been proposed to be a pheromone that induces puberty acceleration in young female mice. These data raise the possibility that some TAARs are pheromone receptors in the nose, a hypothesis consistent with recent data suggesting that the olfactory epithelium contains dedicated pheromone receptors, separate from pheromone receptors in the vomeronasal organ. Future experiments will clarify the roles of TAARs in olfaction.
Dimorphic Olfactory Lobes in the Arthropoda
Authors: Strausfeld Nicholas , Reisenman Carolina E.
Published: July 2009

Specialized olfactory lobe glomeruli relating to sexual or caste differences have been observed in at least five orders of insects, suggesting an early appearance of this trait in insect evolution. Dimorphism is not limited to nocturnal species, but occurs even in insects that are known to use vision for courtship. Other than a single description, there is no evidence for similar structures occurring in the Crustacea, suggesting that the evolution of dimorphic olfactory systems may typify terrestrial arthropods.
Olfactory Impairment in Adults
Authors: Schubert Carla R. , Cruickshanks Karen J. , Murphy Claire , Huang Guan‐Hua , Klein Barbara E. K. , Klein Ronald , Nieto F. Javier , Pankow James S. , Tweed Ted S.
Published: July 2009

Olfactory function may be important for environmental and nutritional safety and enjoyment. Population‐based epidemiological studies of olfaction are needed to understand the magnitude of the health burden, identify modifiable risk factors, and develop and test prevention and treatment strategies for olfactory impairment. However, measuring olfaction in large studies is challenging, requiring repeatable, efficient methods that can measure change over time. Two large cohort studies, the Epidemiology of Hearing Loss Study (EHLS) and the Beaver Dam Offspring Study (BOSS), included olfactory testing. In both studies, the San Diego Odor Identification Test (SDOIT) was used to measure olfaction. Subjects were asked to identify eight common household odors (such as coffee and chocolate). Olfactory impairment was defined as correctly identifying fewer than six out of eight odorants after two trials. The EHLS participants were age 53–95 years at the time of the first measurement (1998–2000), and participants in the BOSS were age 21–84 years. The prevalence of olfactory impairment in the EHLS was 25% overall, more common in men than women, and increased with age. Five years later olfaction was measured a second time and the majority (84%) of the EHLS participants were classified the same. Among those with impairment at the base line nearly one‐third (31%) improved to unimpaired. This heterogeneity in olfactory impairment has unique implications for data analyses and predicting outcomes and associations. Preliminary data from the BOSS suggest the prevalence of olfactory impairment may be lower in younger generations. All these factors point to a continuing need for epidemiological studies of olfaction.
Measuring Taste Impairment in Epidemiologic Studies
Authors: Cruickshanks K. J. , Schubert C. R. , Snyder D. J. , Bartoshuk L. M. , Huang G. H. , Klein B. E. K. , Klein R. , Nieto F. J. , Pankow J. S. , Tweed T. S. , Krantz E. M. , Moy G. S.
Published: July 2009

Taste or gustatory function may play an important role in determining diet and nutritional status and therefore indirectly impact health. Yet there have been few attempts to study the spectrum of taste function and dysfunction in human populations. Epidemiologic studies are needed to understand the impact of taste function and dysfunction on public health, to identify modifiable risk factors, and to develop and test strategies to prevent clinically significant dysfunction. However, measuring taste function in epidemiologic studies is challenging and requires repeatable, efficient methods that can measure change over time. Insights gained from translating laboratory‐based methods to a population‐based study, the Beaver Dam Offspring Study (BOSS) will be shared. In this study, a generalized labeled magnitude scale (gLMS) method was used to measure taste intensity of filter paper disks saturated with salt, sucrose, citric acid, quinine, or 6‐n‐propylthiouracil, and a gLMS measure of taste preferences was administered. In addition, a portable, inexpensive camera system to capture digital images of fungiform papillae and a masked grading system to measure the density of fungiform papillae were developed. Adult children of participants in the population‐based Epidemiology of Hearing Loss Study in Beaver Dam, Wisconsin, are eligible for this ongoing study. The parents were residents of Beaver Dam and 43–84 years of age in 1987–1988; offspring ranged in age from 21–84 years in 2005–2008. Methods will be described in detail and preliminary results about the distributions of taste function in the BOSS cohort will be presented.
Processing Umami and Other Tastes in Mammalian Taste Buds
Authors: Roper Stephen D. , Chaudhari Nirupa
Published: July 2009

Neuroscientists are now coming to appreciate that a significant degree of information processing occurs in the peripheral sensory organs of taste prior to signals propagating to the brain. Gustatory stimulation causes taste bud cells to secrete neurotransmitters that act on adjacent taste bud cells (paracrine transmitters) as well as on primary sensory afferent fibers (neurocrine transmitters). Paracrine transmission, representing cell–cell communication within the taste bud, has the potential to shape the final signal output that taste buds transmit to the brain. The following paragraphs summarize current thinking about how taste signals generally, and umami taste in particular, are processed in taste buds.
Making an Epidermis
Authors: Koster Maranke I.
Published: July 2009

The skin functions as a barrier protecting the body from dehydration and environmental insults. This barrier function is mainly provided by the outermost layer of the skin, the epidermis. The epidermis is maintained by epidermal stem cells which reside in the basal layer and which generate daughter cells that move upward toward the surface of the skin. During this journey, keratinocytes undergo a series of biochemical and morphological changes that result in the formation of the various layers of the epidermis. Eventually, these cells turn into the outermost layer of dead cornified cells that are sloughed into the environment. This review summarizes our current understanding of the mechanisms that control proliferation and differentiation of epidermal stem cells, and thus addresses fundamental processes that control epidermal morphogenesis and function.
Analysis of the Olfactory Mucosa in Chronic Rhinosinusitis
Authors: Yee Karen K. , Pribitkin Edmund A. , Cowart Beverly J. , Rosen David , Feng Pu , Rawson Nancy E.
Published: July 2009

The impact of chronic rhinosinusitis (CRS) on the olfactory mucosa (OM) is dramatic. Cellular profiles and epithelial integrity in OM biopsies were evaluated using histological and immunohistochemical methods to define a strategy for future histological studies of CRS. We have examined nasal biopsies of 54 CRS patients (18–63 years old) and have defined specific histopathological patterns of the OM: normal pseudostratified, goblet cell hyperplasia, squamous metaplasia, and erosion. Goblet cell hyperplasia was most similar to a normal pseudostratified OM pattern but with goblet cells intermixed in the apical layers. Squamous metaplasia exhibited an absence of olfactory supporting cells and had olfactory sensory neurons that were morphologically abnormal. It is unknown if these neurons would be functional in this type of tissue transformation. The pattern of erosion exhibited a severe loss of epithelial layers and a higher prevalence of infiltrating inflammatory cells within the olfactory epithelium when compared to the other OM patterns. Although it is not known if the OM patterns we have noted correspond to specific stages or distinct pathways of the disease, the template proposed here can be used in further studies to understand how the histopathological progression of CRS relates to olfactory loss and the response to treatment.
Parkinson's Disease
Authors: Hawkes Christopher H. , Del Tredici Kelly , Braak Heiko
Published: July 2009

Accumulating evidence suggests that sporadic Parkinson's disease (sPD) has a long prodromal period during which several nonmotor features develop; in particular, impairment of olfaction, vagal dysfunction, and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexuses of the foregut. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (a) nasal, with anterograde progression into the temporal lobe; and (b) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and via transsynaptic transmission reach the preganglionic parasympathetic motor neurons of the vagus nerve. This would allow retrograde transport into the medulla and from here into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sPD is pathogenic access to the brain through the foregut and nose—hence the term “dual hit.”
Multimodal Sensory Integration of Courtship Stimulating Cues in Drosophila melanogaster
Authors: Griffith Leslie C. , Ejima Aki
Published: July 2009

Mechanisms for identifying appropriate mating partners are required for any species to survive. In many types of animals, males employ multiple sensory modalities to initially search for females and to subsequently determine if they are fit and/or receptive. In this paper we will detail the multiple types of sensory information that are used to initiate and drive courtship in Drosophila melanogaster and discuss the importance of context in the interpretation of chemosensory cues. We find that food‐related olfactory cues increase the salience of the aversive pheromone cis‐vaccenyl acetate.
Food Consumption Inhibits Pain‐related Behaviors
Authors: Mason Peggy , Foo H.
Published: July 2009

The function of the endogenous analgesia system under natural circumstances has been little explored. Our recent work shows that animals are significantly less responsive to noxious stimulation during slow wave sleep, micturition, and while eating than during quiet wake. The analgesia associated with eating is dependent on activity in the medullary raphe magnus, the final common brain stem region in endogenous analgesia pathways. Eating analgesia does not depend on energy‐depletion due to food deprivation. Further, analgesia accompanies chow‐eating even though chow has no sucrose, demonstrating that sucrose is not a necessary component of analgesia‐evoking ingestates. Since raphe magnus modulates processing of innocuous as well as nociceptive information, the sensory suppression accompanying eating is likely a more general depression of the response to external stimulation. Such a phenomenon would serve animals well under natural conditions where energy‐dense food is scarce but has counterproductive effects, possibly contributing to obesity, in modern human society where energy‐dense food is readily available.
The Role of Foxg1 in the Development of Neural Stem Cells of the Olfactory Epithelium
Authors: Kawauchi Shimako , Santos Rosaysela , Kim Joon , Hollenbeck Piper L. W. , Murray Richard C. , Calof Anne L.
Published: July 2009

The olfactory epithelium (OE) of the mouse is an excellent model system for studying principles of neural stem cell biology because of its well‐defined neuronal lineage and its ability to regenerate throughout life. To approach the molecular mechanisms of stem cell regulation in the OE, we have focused on Foxg1, also known as brain factor 1, which is a member of the Forkhead transcription factor family. Foxg1−/− mice show major defects in the OE at birth, suggesting that Foxg1 plays an important role in OE development. We find that Foxg1 is expressed in cells within the basal compartment of the OE, the location where OE stem and progenitor cells are known to reside. Since FoxG1 is known to regulate proliferation of neuronal progenitor cells during telencephalon development, we performed bromodeoxyuridine pulse–chase labeling of Sox2‐expressing neural stem cells during primary OE neurogenesis. We found the percentage of Sox2‐expressing cells that retained bromodeoxyuridine was twice as high in Foxg1−/− OE cells as in the wild type, suggesting that these cells are delayed and/or halted in their development in the absence of Foxg1. Our findings suggest that the proliferation and/or subsequent differentiation of Sox2‐expressing neural stem cells in the OE is regulated by Foxg1.
Need for Related Multipronged Approaches to Understand Olfactory Bulb Signal Processing
Authors: Restrepo Diego , Whitesell Jennifer , Doucette Wilder
Published: July 2009

Recent work from our laboratory in awake behaving animals shows that olfactory bulb processing changes depending profoundly on behavioral context. Thus, we find that when recording from the olfactory bulb in a mouse during a go–no go association learning task, it is not unusual to find a mitral cell that initially does not respond to the rewarded or unrewarded odors but develops a differential response to the stimuli during the learning session. This places a challenge on how to approach understanding of olfactory bulb processing, because neural interactions differ depending on the status of the animal. Here we address the question of how the different approaches to study olfactory bulb neuron responses, including studies in anesthetized and unanesthetized animals in vivo and recordings in slices, complement each other. We conclude that more critical understanding of the relationship between the measurements in the different preparations is necessary for future advances in the understanding of olfactory bulb processing of odor information.
A High‐Throughput Screen for Chemicals that Increase the Lifespan of Caenorhabditis elegans
Authors: Petrascheck Michael , Ye Xiaolan , Buck Linda B.
Published: July 2009

One long‐term goal of aging research is to find drugs that can delay aging and the onset of age‐associated diseases. With this in mind, we screened 88,000 chemicals for the ability to increase the lifespan of Caenorhabditis elegans nematodes. We found that mianserin, a serotonin receptor antagonist used as an antidepressant in humans, can increase C. elegans lifespan when given only during adulthood. This effect is reduced or abolished by mutations that affect serotonin synthesis or serotonin reuptake at synapses. It also requires a serotonin receptor and an octopamine receptor, both of which are inhibited by the drug. Mianserin has no effect on the lifespan of animals with increased longevity due to dietary restriction or with a mutation that reduces food intake, indicating that the drug extends lifespan via mechanisms linked to dietary restriction. These studies indicate that lifespan can be increased by inhibiting certain kinds of neurotransmission previously implicated in food sensing, possibly by mimicking a physiological state associated with dietary restriction.
Inflammation and Taste Disorders
Authors: Wang Hong , Zhou Minliang , Brand Joseph , Huang Liquan
Published: July 2009

Taste disorders, including taste distortion and taste loss, negatively impact general health and quality of life. To understand the underlying molecular and cellular mechanisms, we set out to identify inflammation‐related molecules in taste tissue and to assess their role in the development of taste dysfunctions. We found that 10 out of 12 mammalian Toll‐like receptors (TLRs), type I and II interferon (IFN) receptors, and their downstream signaling components are present in taste tissue. Some TLRs appear to be selectively or more abundantly expressed in taste buds than in nongustatory lingual epithelium. Immunohistochemistry with antibodies against TLRs 1, 2, 3, 4, 6, and 7 confirmed the presence of these receptor proteins in taste bud cells, of which TLRs 2, 3, and 4 are expressed in the gustducin‐expressing type II taste bud cells. Administration of TLR ligands, lipopolysaccharide, and double‐stranded RNA polyinosinic:polycytidylic acid, which mimics bacterial or viral infection, activates the IFN signaling pathways, upregulates the expression of IFN‐inducible genes, and downregulates the expression of c‐fos in taste buds. Finally, systemic administration of IFNs augments apoptosis of taste bud cells in mice. Taken together, these data suggest that TLR and IFN pathways function collaboratively in recognizing pathogens and mediating inflammatory responses in taste tissue. This process, however, may interfere with normal taste transduction and taste bud cell turnover and contributes to the development of taste disorders.
Associations between the Ability to Detect a Bitter Taste, Dietary Behavior, and Growth
Authors: Golding Jean , Steer Colin , Emmett Pauline , Bartoshuk Linda M. , Horwood Jeremy , Smith George Davey
Published: July 2009

Information from the Avon Longitudinal Study of Parents and Children (ALSPAC) has been used to assess the relationships between the 10‐year‐old child's response to a bitter taste test using PROP, features of early childhood feeding characteristics and 10‐year‐old height, weight, and body mass index. Children who were tasters (75% of sample) were slightly more likely to have been described as fussy eaters than the nontasters, and the supertasters were more likely to be in the lowest height decile at age 10.
Development and Regeneration of the Inner Ear
Authors: Kwan Tao , White Patricia M. , Segil Neil
Published: July 2009

Loss of sensory hair cells is the leading cause of deafness in humans. The mammalian cochlea cannot regenerate its complement of sensory hair cells. Thus at present, the only treatment for deafness due to sensory hair cell loss is the use of prosthetics, such as hearing aids and cochlear implants. In contrast, in nonmammalian vertebrates, such as birds, hair cell regeneration occurs following the death of hair cells and leads to the restoration of hearing. Regeneration in birds is successful because supporting cells that surround the hair cells can divide and are able to subsequently differentiate into new hair cells. However, supporting cells in mammals do not normally divide or transdifferentiate when hair cells are lost, and so regeneration does not occur. To understand the failure of mammalian cochlear hair cell regeneration, we need to understand the molecular mechanisms that underlie cell division control and hair cell differentiation, both during embryogenesis and in the postnatal mouse. In this review, we present a discussion of the regulation of cell proliferation in embryogenesis and during postnatal maturation. We also discuss the role of the Cip/Kip cell cycle inhibitors and Notch signaling in the control of stability of the differentiated state of early postnatal supporting cells. Finally, recent data indicate that some early postnatal mammalian supporting cells retain a latent capacity to divide and transdifferentiate into sensory hair cells. Together, these observations make supporting cells important therapeutic targets for continued efforts to induce hair cell regeneration.
The Genetics of Bitterness and Pungency Detection and Its Impact on Phytonutrient Evaluation
Authors: Des Gachons Catherine Peyrot , Beauchamp Gary K. , Breslin Paul A. S.
Published: July 2009

Perceptions of food vary as a function of an individual's genetic factors, such as the set of alleles coding for their taste, irritation, and olfaction receptor proteins. We established a direct link between individual differences in sensitivity to the glucosinolates, a family of bitter compounds in vegetables and roots, and genetic variations in the bitter taste receptor (hTAS2R38) for these compounds. These individual differences in the perception of nutrients likely evolved to influence ingestion. Bitterness and pungency are both believed to signal potentially harmful compounds in our foods, but consumption of many compounds eliciting these sensations is also linked to decreased risks of cancer and degenerative and cardiovascular diseases, implicating the medicinal values of these compounds as well. Since almost all medicines are toxic at high doses, the phytonutrients may be considered both toxins and medicines, depending on the individual's metabolic sensitivities. The conflicting harmful and healthful effects of bitter and pungent compounds might explain why human populations maintain heterozygosity in sensory receptor genes underlying these sensations.