Showing papers on "Olfactory system published in 2017"
TL;DR: Genetic and neurobiological data that reveal features unique to the human olfactory system are regularly misinterpreted to underlie the putative microsmaty, and the impact of human Olfactory dysfunction is underappreciated in medical practice.
Abstract: BACKGROUND It is widely believed that the human sense of smell is inferior to that of
other mammals, especially rodents and dogs. This Review traces the
scientific history of this idea to 19th-century neuroanatomist Paul Broca.
He classified humans as “nonsmellers” not owing to any sensory
testing but because he believed that the evolutionary enlargement of the
human frontal lobe gave human beings free will at the expense of the
olfactory system. He especially emphasized the small size of the human
brain’s olfactory bulb relative to the size of the brain overall, and
noted that other mammals have olfactory bulbs that are proportionately much
larger. Broca’s claim that humans have an impoverished olfactory
system (later labeled “microsmaty,” or tiny smell) influenced
Sigmund Freud, who argued that olfactory atrophy rendered humans susceptible
to mental illness. Humans’ supposed microsmaty led to the scientific
neglect of the human olfactory system for much of the 20th century, and even
today many biologists, anthropologists, and psychologists persist in the
erroneous belief that humans have a poor sense of smell. Genetic and
neurobiological data that reveal features unique to the human olfactory
system are regularly misinterpreted to underlie the putative microsmaty, and
the impact of human olfactory dysfunction is underappreciated in medical
practice. ADVANCES Although the human olfactory system has turned out to have some biological
differences from that of other mammalian species, it is generally similar in
its neurobiology and sensory capabilities. The human olfactory system has
fewer functional olfactory receptor genes than rodents, for instance, but
the human brain has more complex olfactory bulbs and orbitofrontal cortices
with which to interpret information from the roughly 400 receptor types that
are expressed. The olfactory bulb is proportionately smaller in humans than
in rodents, but is comparable in the number of neurons it contains and is
actually much larger in absolute terms. Thus, although the rest of the brain
became larger as humans evolved, the olfactory bulb did not become smaller.
When olfactory performance is compared experimentally between humans and
other animals, a key insight has been that the results are strongly
influenced by the selection of odors tested, presumably because different
odor receptors are expressed in each species. When an appropriate range of
odors is tested, humans outperform laboratory rodents and dogs in detecting
some odors while being less sensitive to other odors. Like other mammals,
humans can distinguish among an incredible number of odors and can even
follow outdoor scent trails. Human behaviors and affective states are also
strongly influenced by the olfactory environment, which can evoke strong
emotional and behavioral reactions as well as prompting distinct memories.
Odor-mediated communication between individuals, once thought to be limited
to “lower animals,” is now understood to carry information
about familial relationships, stress and anxiety levels, and reproductive
status in humans as well, although this information is not always
consciously accessible. OUTLOOK The human olfactory system is increasingly understood to be highly dynamic.
Olfactory sensitivity and discrimination abilities can be changed by
experiences like environmental odor exposure or even just learning to
associate odors with other stimuli in the laboratory. The neurobiological
underpinnings of this plasticity, including “bottom-up”
factors like regulation of peripheral odor receptors and
“top-down” factors like the sensory consequences of emotional
and cognitive states, are just beginning to be understood. The role of
olfactory communication in shaping social interactions is also actively
being explored, including the social spread of emotion through olfactory
cues. Finally, impaired olfaction can be a leading indicator of certain
neurodegenerative diseases, notably Parkinson’s disease and
Alzheimer’s disease. New experimentation will be required to
understand how olfactory sequelae might also reflect problems elsewhere in
the nervous system, including mental disorders with sensory symptomatology.
The idea that human smell is impoverished compared to other mammals is a
19th-century myth.
480 citations
TL;DR: Whether damage to such a substrate is the basis for the perceptual differences in olfaction or whether disease-specific or other entities, such as respiratory infections or pollution, are responsible might provide crucial insight into the cause of disease pathology at its earliest stages of development.
Abstract: Summary In patients with neurodegenerative diseases, there is a spectrum of smell dysfunction ranging from severe loss, as seen in Alzheimer's disease and Parkinson's disease, to relatively little loss, as seen in progressive supranuclear palsy. Given the ubiquitous but varying degrees of olfactory dysfunction among such diseases, it is conceivable that differential disruption of a common primordial neuropathological substrate causes these differences in olfactory function. For example, the amount of damage to forebrain neurotransmitter and neuromodulator circuits, most notably those involving cholinergic transmission, appears to be correlated with quantitative smell test scores across a wide range of neurodegenerative diseases. Thus, a key question is whether damage to such a substrate is the basis for the perceptual differences in olfaction or whether disease-specific or other entities, such as respiratory infections or pollution, are responsible. In light of the early preclinical onset of smell deficits in many neurodegenerative diseases, the answer to this question might provide crucial insight into the cause of disease pathology at its earliest stages of development.
325 citations
TL;DR: It is established that neuronal transcriptomic identity corresponds with anatomical and physiological identity defined by connectivity and function, and a new lineage-specific transcription factor is identified that instructs PN dendrite targeting.
274 citations
TL;DR: The existing literature on olfactory function in Parkinson’s disease is summarized, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.
Abstract: Olfactory dysfunction is common in Parkinson’s disease (PD) and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histologic hallmark of PD, in the olfactory bulb. Clinical tests are available that allow for the rapid characterization of olfactory dysfunction, including tests of odor identification, discrimination, detection, and recognition thresholds, memory, and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations. The high prevalence of olfactory impairment, along with the ease and low cost of assessment, has fostered great interest in olfaction as a potential biomarker for PD. Hyposmia may help differentiate PD from other causes of parkinsonism, and may also aid in the identification of “pre-motor” PD due to the early pathologic involvement of olfactory pathways. Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline. In this article, we summarize the existing literature on olfaction in PD, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.
260 citations
TL;DR: A significant, positive effect of olfactory training is found for all Olfactory abilities, with large effects of training on identification, discrimination and TDI-score and small-to-moderate effect in the case of threshold for odor detection.
Abstract: The neural plasticity of the olfactory system offers possibilities of treatment in terms of stimulation of the sense of smell, and different studies have suggested effectiveness of smell training, i.e., daily exposition to certain odors. To obtain reliable and precise estimates of overall treatment benefit on the olfactory function, we meta-analyzed the effects of smell training reported in 13 previous studies. We analyzed the smell training effectiveness across three different olfactory abilities, smell identification, discrimination and threshold for odor detection. We found a significant, positive effect of olfactory training for all olfactory abilities, with large effects of training on identification, discrimination and TDI-score and small-to-moderate effect in the case of threshold for odor detection. Interestingly, the pattern of results differed across Sniffin Sticks subtests depending on the origin of participants smell disorder, and the smell training duration influenced its effectiveness in the case of identification and the TDI score. Although the exact mechanism of olfactory recovery following the smell training still requires further investigation, our meta-analysis showed that such training should be considered an addition or alternative to existing smell treatment methods.
215 citations
TL;DR: It is suggested that olfaction and depression interact in two ways: first, olfactory function in depression is impaired as a consequence of reducedOlfactory attention and diminished olfatory receptor turnover rates; and second, the OB may constitute a marker for enhanced vulnerability to depression.
Abstract: Olfactory and emotional higher processing pathways share common anatomical substrates. Hence, depression is often accompanied by alterations in olfactory function. These alterations are negative in nature and may involve decreased activation in olfactory eloquent structures or decreased volume in the olfactory bulb (OB). We suggest that olfaction and depression interact in two ways. First, olfactory function in depression is impaired as a consequence of reduced olfactory attention and diminished olfactory receptor turnover rates. Second, the OB may constitute a marker for enhanced vulnerability to depression. Closer analysis of these interactions may help to explain observed experimental data, as well as to elucidate new therapeutic strategies involving olfaction. Because of the difficulties to disentangle cause from consequence in the relationship between olfaction and depression, longitudinal and intervention studies are necessary to elucidate this further.
201 citations
TL;DR: Using large-scale population recordings in awake mice, distinct coding strategies facilitate non-interfering representations of odor identity and intensity in piriform cortex that reveal complementary coding strategies that can selectively represent distinct features of a stimulus.
Abstract: The ability to represent both stimulus identity and intensity is fundamental for perception. Using large-scale population recordings in awake mice, we find distinct coding strategies facilitate non-interfering representations of odor identity and intensity in piriform cortex. Simply knowing which neurons were activated is sufficient to accurately represent odor identity, with no additional information about identity provided by spike time or spike count. Decoding analyses indicate that cortical odor representations are not sparse. Odorant concentration had no systematic effect on spike counts, indicating that rate cannot encode intensity. Instead, odor intensity can be encoded by temporal features of the population response. We found a subpopulation of rapid, largely concentration-invariant responses was followed by another population of responses whose latencies systematically decreased at higher concentrations. Cortical inhibition transforms olfactory bulb output to sharpen these dynamics. Our data therefore reveal complementary coding strategies that can selectively represent distinct features of a stimulus.
201 citations
TL;DR: It is reported that lateral EC projection neurons selectively form direct excitatory synapses onto a subpopulation of morphologically complex, calbindin-expressing pyramidal cells in the dorsal CA1 (dCA1), while medial EC neurons uniformly innervate all dCA1 PCs.
Abstract: Entorhinal cortex transfers multimodal information to hippocampus CA1 neurons via indirect and direct pathways. The authors show that excitatory projections from lateral entorhinal cortex selectively target a subpopulation of morphologically complex, calbindin-expressing pyramidal cells in CA1, forming a distinct direct circuit that is required for olfactory associative learning.
198 citations
TL;DR: It is demonstrated that mice upon conditional ablation of mature olfactory sensory neurons (OSNs) are resistant to diet-induced obesity accompanied by increased thermogenesis in brown and inguinal fat depots, unraveling a new bidirectional function for the o aroma system in controlling energy homeostasis in response to sensory and hormonal signals.
174 citations
TL;DR: Calcium imaging is used to determine how odor identity is encoded in olfactory cortex and it is proposed that distinct perceptual features of odors are encoded in independent subnetworks of neurons in the o aroma cortex.
Abstract: Olfactory perception and behaviors critically depend on the ability to identify an odor across a wide range of concentrations. Here, we use calcium imaging to determine how odor identity is encoded in olfactory cortex. We find that, despite considerable trial-to-trial variability, odor identity can accurately be decoded from ensembles of co-active neurons that are distributed across piriform cortex without any apparent spatial organization. However, piriform response patterns change substantially over a 100-fold change in odor concentration, apparently degrading the population representation of odor identity. We show that this problem can be resolved by decoding odor identity from a subpopulation of concentration-invariant piriform neurons. These concentration-invariant neurons are overrepresented in piriform cortex but not in olfactory bulb mitral and tufted cells. We therefore propose that distinct perceptual features of odors are encoded in independent subnetworks of neurons in the olfactory cortex.
142 citations
TL;DR: A novel model in which multiple interneuron types with distinct abundances, connectivity patterns, and physiologies complement one another to regulate M/TC activity and sensory processing is yields a novel model.
Abstract: Synaptic inhibition critically influences sensory processing throughout the mammalian brain, including the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system...
TL;DR: This review of sensory coding from the vinegar fly Drosophila melanogaster will outline the relevant steps of the olfactory code and describe its progress along the Olfactory pathway, i.e., from the peripheral ofactory organs to the first olf factory center in the brain and then to the higher processing areas where the odor perception takes place, enabling an organism to make odor-guided decisions.
Abstract: Sensory coding represents a basic principle of all phyla in nature: species attempt to perceive their natural surroundings and to make sense of them. Ultimately, sensory coding is the only way to allow a species to make the kinds of crucial decisions that lead to a behavioral response. In this manner, animals are able to detect numerous parameters, ranging from temperature and humidity to light and sound to volatile or non-volatile chemicals. Most of these environmental cues represent a clearly defined stimulus array that can be described along a single physical parameter, such as wavelength or frequency; odorants, in contrast, cannot. The odor space encompasses an enormous and nearly infinite number of diverse stimuli that cannot be classified according to their positions along a single dimension. Hence, the olfactory system has to encode and translate the vast odor array into an accurate neural map in the brain. In this review, we will outline the relevant steps of the olfactory code and describe its progress along the olfactory pathway, i.e., from the peripheral olfactory organs to the first olfactory center in the brain and then to the higher processing areas where the odor perception takes place, enabling an organism to make odor-guided decisions. We will focus mainly on studies from the vinegar fly Drosophila melanogaster, but we will also indicate similarities to and differences from the olfactory system of other invertebrate species as well as of the vertebrate world.
TL;DR: To the authors' knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipOSE tissue and shifting the fuel preference to fats in the Liver and BAT.
Abstract: Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats. After 6 weeks of administration, mice fed a high-fat diet (HFD) exhibited a marked reduction in adiposity. AzA treatment induced expression of PPAR-α and genes required for FAO in the liver and induced the expression of PPAR-γ coactivator 1-α (Ppargc1a) and uncoupling protein-1 (Ucp1) genes in brown adipose tissue (BAT). Moreover, treatment with AzA increased insulin sensitivity and ketone body levels. This led to a reduction in the respiratory quotient and an increase in the FAO rate, as indicated by indirect calorimetry. AzA treatment had similar antiobesogenic effects in HFD-fed ob/ob mice. Importantly, AzA-associated metabolic changes were completely abrogated in HFD-fed Olfr544-/- mice. To our knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting the fuel preference to fats in the liver and BAT.
TL;DR: Intranasal vitamin A at a dose of 10,000 IU per day for 2 months may be useful in the treatment of post-infectious olfactory loss and further work with prospective, placebo-controlled studies is required to confirm these findings.
Abstract: Vitamin A plays a decisive role in the regeneration of olfactory receptor neurons. In this retrospective study we investigated the effectiveness of topical vitamin A in patients with post-infectious and posttraumatic smell disorders. Retrospective cohort. A total of 170 patients (age range 18–70 years, mean age 52 years) participated. Forty-six patients were treated with smell training only. The remaining 124 patients received smell training and topical vitamin A. Olfactory function was assessed using the Sniffin’ Sticks test kit, a validated technique to measure odor thresholds, discrimination and identification. The duration of olfactory training was 12 weeks. In patients receiving vitamin A, this was applied topically (head back position) at a dose of 10,000 IU/day for 8 weeks. Follow-up testing was performed approximately 10 months after the first assessment. Thirty-seven per cent of all post-infectious patients treated with vitamin A exhibited clinical improvement, whereas only 23% improved in controls. Using a Chi-square test, this was a significant result (χ
2 = 7.06, df = 2, p = 0.03). In addition, when comparing change in score after treatment, olfactory training + vitamin A produced significantly greater improvement compared with training alone, in discrimination score for all patients (1.4 points, p = 0.008), and in threshold and discrimination in the post-infectious group (1.6 points, p = 0.01 and 1.4 points, p = 0.04, respectively). Intranasal vitamin A at a dose of 10,000 IU per day for 2 months may be useful in the treatment of post-infectious olfactory loss. Further work with prospective, placebo-controlled studies is required to confirm these findings.
TL;DR: The deletion of BmOrco gene in the Lepidopteran model insect, Bombyx mori, using a binary transgene-based clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 system provides insights into the insect olfactory system and provides a paradigm for agroforestry pest control.
TL;DR: Data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in Olfactory bulb volume.
Abstract: Repeated exposure to odors modifies olfactory function. Consequently, "olfactory training" plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19-43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the "Sniffin' Sticks" test battery.OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.
TL;DR: Using intracranial EEG recordings from rare patients with medically resistant epilepsy, it is found that theta oscillations are a distinct electrophysiological signature of olfactory processing in the human brain and human piriform cortex can utilize these signals to rapidly differentiate odor stimuli.
TL;DR: The no-odor condition, allowing investigation of activation patterns when the peripheral olfactory system was not directly involved, elicited the same functional response as the odor condition for each of the three groups, indicating that the olfFactory activation deficits present in AD and MCI patients are most likely caused by degeneration of the central Olfactory nervous system.
Abstract: BACKGROUND Olfactory deficits are present in early Alzheimer's disease (AD) and mild cognitively impaired (MCI) patients. However, whether these deficits are due to dysfunction of the central or peripheral olfactory nervous system remains uncertain. This question is fundamentally important for developing imaging biomarkers for AD using olfactory testing. OBJECTIVE This study sought to use olfactory functional magnetic resonance imaging (fMRI) to further demonstrate the involvement of the central olfactory system in olfactory deficits in MCI and AD. METHODS We investigated the central olfactory system in 27 cognitively normal controls (CN), 21 MCI, and 15 AD subjects using olfactory fMRI with an odor-visual association paradigm during which a visual cue was paired with lavender odorant (odor condition) or odorless air (no-odor condition). RESULTS The CN subjects had significantly greater activated volume in the primary olfactory cortex during both the odor and no-odor conditions compared to either the MCI or AD groups (p < 0.05). No significant differences were observed between the odor and no-odor conditions within each group. No-odor condition activation in AD and MCI correlated with the cognitive and olfactory assessments. CONCLUSION The no-odor condition, allowing investigation of activation patterns when the peripheral olfactory system was not directly involved, elicited the same functional response as the odor condition for each of the three groups. Thus, the olfactory activation deficits present in AD and MCI patients are most likely caused by degeneration of the central olfactory nervous system.
TL;DR: An analysis of data obtained by a systematic literature review regarding the possible association between olfaction and ASDs suggested a possible involvement of olfactory impairment in ASDs, underlining the importance of Olfactory evaluation in the clinical assessment of ASDs.
Abstract: Olfactory function is a well-known early biomarker for neurodegeneration and neural functioning in the adult population, being supported by a number of brain structures that could be dysfunctioning in neurodegenerative processes. Evidence has suggested that atypical sensory and, particularly, olfactory processing is present in several neurodevelopmental conditions, including autism spectrum disorders (ASDs). In this paper, we present data obtained by a systematic literature review, conducted according to PRISMA guidelines, regarding the possible association between olfaction and ASDs, and analyze them critically in order to evaluate the occurrence of olfactory impairment in ASDs, as well as the possible usefulness of olfactory evaluation in such conditions. The results obtained in this analysis suggested a possible involvement of olfactory impairment in ASDs, underlining the importance of olfactory evaluation in the clinical assessment of ASDs. This assessment could be potentially included as a complementary evaluation in the diagnostic protocol of the condition. Methods for study selection and inclusion criteria were specified in advance and documented in PROSPERO protocol #CRD42014013939.
TL;DR: This work used large-scale serial section electron microscopy to reconstruct all the olfactory receptor neuron (ORN) axons that target a left-right pair of glomeruli, as well as all the projection neurons (PNs) postsynaptic to these ORNs, and found three variations in ORN→PN connectivity.
Abstract: Neural network function can be shaped by varying the strength of synaptic connections. One way to achieve this is to vary connection structure. To investigate how structural variation among synaptic connections might affect neural computation, we examined primary afferent connections in the Drosophila olfactory system. We used large-scale serial section electron microscopy to reconstruct all the olfactory receptor neuron (ORN) axons that target a left-right pair of glomeruli, as well as all the projection neurons (PNs) postsynaptic to these ORNs. We found three variations in ORN→PN connectivity. First, we found a systematic co-variation in synapse number and PN dendrite size, suggesting total synaptic conductance is tuned to postsynaptic excitability. Second, we discovered that PNs receive more synapses from ipsilateral than contralateral ORNs, providing a structural basis for odor lateralization behavior. Finally, we found evidence of imprecision in ORN→PN connections and show how this can diminish network performance.
TL;DR: The medial part of the olfactory tubercle was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool, and the results revealed many unique connecting features.
Abstract: The medial part of the olfactory tubercle (OT) is a brain structure located at the interface of the reward and olfactory system. It is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. However, the structure of the anatomic circuitry of the medial part of the OT is still unclear. In the present study, the medial part of the OT was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. In order to further investigate the detailed connections for specific neurons, another tracing tool - rabies virus was utilized for D1R-cre and D2R-cre mice. The D1R and D2R neurons in the medial part of the OT were both preferentially innervated by the olfactory areas, especially the piriform cortex, and both had similar direct input patterns. With the help of the adeno-associated virus labeling, it was found that the two subpopulations of neurons primarily innervate with the reward related brain regions, with slightly less axons projecting to the olfactory areas. Thus, the whole-brain input and output circuitry structures for specific types of neurons in the medial part of the OT were systematically investigated, and the results revealed many unique connecting features. This work could provide new insights for further study into the physiological functions of the medial part of the OT.
TL;DR: It is shown that protracted exposure to kin or non-kin odorants changes the number of dopamine (DA)- or gamma aminobutyric acid (GABA)-expressing neurons, with corresponding changes in attraction/aversion behavior.
TL;DR: Recent findings on nutrient-sensing neurons in olfactory areas are summarized and the limits of knowledge are delineated, which could contribute to determining the etiology of metabolic disorders.
Abstract: Olfaction is a major sensory modality involved in real time perception of the chemical composition of the external environment. Olfaction favors anticipation and rapid adaptation of behavioral responses necessary for animal survival. Furthermore, recent studies have demonstrated that there is a direct action of metabolic peptides on the olfactory network. Orexigenic peptides such as ghrelin and orexin increase olfactory sensitivity, which in turn, is decreased by anorexigenic hormones such as insulin and leptin. In addition to peptides, nutrients can play a key role on neuronal activity. Very little is known about nutrient sensing in olfactory areas. Nutrients, such as carbohydrates, amino acids, and lipids, could play a key role in modulating olfactory sensitivity to adjust feeding behavior according to metabolic need. Here we summarize recent findings on nutrient-sensing neurons in olfactory areas and delineate the limits of our knowledge on this topic. The present review opens new lines of investigations on the relationship between olfaction and food intake, which could contribute to determining the etiology of metabolic disorders.
TL;DR: Olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long‐term use of analgesics compared to age‐matched healthy controls is investigated.
TL;DR: The molecular mechanisms that determine the regenerative capacity of stem cells, and the ability of newly generated neurons in directing their axons toward specific targets, remain elusive.
TL;DR: Applications of a new method to process mouse heads for microscopy by sectioning, mounting, and staining whole skulls enabled new discoveries related to α-synuclein expression and its function in mice, including PD- and AD-linked gene expression in the olfactory system.
Abstract: Braak and Del Tredici have proposed that typical Parkinson disease (PD) has its origins in the olfactory bulb and gastrointestinal tract. However, the role of the olfactory system has insufficiently been explored in the pathogeneses of PD and Alzheimer disease (AD) in laboratory models. Here, we demonstrate applications of a new method to process mouse heads for microscopy by sectioning, mounting, and staining whole skulls ('holocranohistochemistry'). This technique permits the visualization of the olfactory system from the nasal cavity to mitral cells and dopamine-producing interneurons of glomeruli in the olfactory bulb. We applied this method to two specific goals: first, to visualize PD- and AD-linked gene expression in the olfactory system, where we detected abundant, endogenous α-synuclein and tau expression in the olfactory epithelium. Furthermore, we observed amyloid-β plaques and proteinase-K-resistant α-synuclein species, respectively, in cranial nerve-I of APP- and human SNCA-over-expressing mice. The second application of the technique was to the modeling of gene-environment interactions in the nasal cavity of mice. We tracked the infection of a neurotropic respiratory-enteric-orphan virus from the nose pad into cranial nerves-I (and -V) and monitored the ensuing brain infection. Given its abundance in the olfactory epithelia, we questioned whether α-synuclein played a role in innate host defenses to modify the outcome of infections. Indeed, Snca-null mice were more likely to succumb to viral encephalitis versus their wild-type littermates. Moreover, using a bacterial sepsis model, Snca-null mice were less able to control infection after intravenous inoculation with Salmonella typhimurium. Together, holocranohistochemistry enabled new discoveries related to α-synuclein expression and its function in mice. Future studies will address: the role of Mapt and mutant SNCA alleles in infection paradigms; the contribution of xenobiotics in the initiation of idiopathic PD; and the safety to the host when systemically targeting α-synuclein by immunotherapy.
TL;DR: The olfactory bulb of zebrafish larvae for activated neurons located at the sole glomerulus mdG2 which receives crypt cell input is investigated to show a neuronal circuit from crypt/microvillous Olfactory sensory neurons via dorsomedial ofactory bulb and intermediate ventral telencephalic nucleus to tuberal hypothalamus, demonstrating for the first time an accessory o aroma system in teleosts.
Abstract: Zebrafish larvae imprint on visual and olfactory cues of their kin on day 5 and 6 postfertilization, respectively. Only imprinted (but not non-imprinted) larvae show strongly activated crypt (and some microvillous) cells demonstrated by pERK levels after subsequent exposure to kin odor. Here, we investigate the olfactory bulb of zebrafish larvae for activated neurons located at the sole glomerulus mdG2 which receives crypt cell input. Imprinted larvae show a significantly increased activation of olfactory bulb cells compared to non-imprinted larvae after exposure to kin odor. Surprisingly, pERK activated Orthopedia-positive cell numbers in the intermediate ventral telencephalic nucleus were higher in non-imprinted, kin odor stimulated larvae compared to control and to kin-odor stimulated imprinted larvae and control. Moreover, DiI tracing experiments in adult zebrafish show a neuronal circuit from crypt/microvillous olfactory sensory neurons via dorsomedial olfactory bulb and intermediate ventral telencephalic nucleus (thus, arguably the teleostean medial amygdala) to tuberal hypothalamus, demonstrating for the first time an accessory olfactory system in teleosts.
TL;DR: Olfactory loss over time in PD and controls is similar, but there is significant correlation between this loss and basal ganglia volumes only in patients, and this loss is observed in patients only.
TL;DR: The differential diagnosis, workup, and current treatment strategies of anosmia and smell disorders are reviewed, with a focus on improving both the diagnosis and reporting of treatment outcomes of olfactory training.
Abstract: The ability to scrutinize our surroundings remains heavily dependent on the sense of smell. From the ability to detect dangerous situations such as fires to the recollection of a fond memory triggered by an odor, the advantages of an intact olfactory system cannot be overstated. Outcomes studies have highlighted the profound negative impact of anosmia and parosmia on the overall quality of life. The National Institute on Deafness and Other Communication Disorders estimates that ∼1.4% of the United States population experiences chronic olfactory dysfunction and smell loss. Efforts have focused on improving both the diagnosis of olfactory dysfunction through olfactory testing and improved reporting of treatment outcomes of olfactory training. The purpose of this article was to review the differential diagnosis, workup, and current treatment strategies of anosmia and smell disorders.
TL;DR: Functional disconnectivity of olfactory regions in schizophrenia is suggested, which may account for Olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia.
Abstract: Background Evidence for olfactory dysfunction in schizophrenia has been firmly established However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia Methods We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia Results The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices Conclusions The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia