The Smell, That Forgotten Sense
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Distinct Representations of Olfactory Information in Different Cortical Centres
LETTER doi:10.1038/nature09868 Distinct representations of olfactory information in different cortical centres Dara L. Sosulski1, Maria Lissitsyna Bloom1{, Tyler Cutforth1{, Richard Axel1 & Sandeep Robert Datta1{ Sensory information is transmitted to the brain where it must be behaviours, but is unlikely to specify innate behaviours. Rather, innate processed to translate stimulus features into appropriate beha- olfactory behaviours are likely to result from the activation of genetically vioural output. In the olfactory system, distributed neural activity determined, stereotyped neural circuits. We have therefore developed a in the nose is converted into a segregated map in the olfactory strategy to trace the projections from identified glomeruli in the olfactory bulb1–3. Here we investigate how this ordered representation is bulb to higher olfactory cortical centres. transformed in higher olfactory centres in mice. We have Mitral and tufted cells that innervate a single glomerulus were developed a tracing strategy to define the neural circuits that labelled by electroporation of tetramethylrhodamine (TMR)-dextran convey information from individual glomeruli in the olfactory under the guidance of a two-photon microscope. This technique labels bulb to the piriform cortex and the cortical amygdala. The spatial mitral and tufted cells that innervate a single glomerulus and is suffi- order in the bulb is discarded in the piriform cortex; axons from ciently robust to allow the identification of axon termini within mul- individual glomeruli project diffusely to the piriform without tiple higher order olfactory centres (Figs 1a–c, 2 and Supplementary apparent spatial preference. In the cortical amygdala, we observe Figs 1–4). Labelling of glomeruli in the olfactory bulbs of mice that broad patches of projections that are spatially stereotyped for indi- express GFP under the control of specific odorant receptor promoters vidual glomeruli. -
Dense Representation of Natural Odorants in the Mouse Olfactory Bulb
BRIEF COMMUNICATIONS Dense representation of Online Methods), leading to a reduced number of activated glomeruli (n = 6 odorant-mouse pairs, paired t test, P < 0.005; Fig. 1e). natural odorants in the mouse We then applied 40 different natural odorants using the olfactom- eter to minimize the animal’s stress and to have a better temporal olfactory bulb control of the odorant application. In all of the mice that we tested (n = 8), every odorant evoked a specific dense pattern of glomerular Roberto Vincis1,2, Olivier Gschwend1–3, Khaleel Bhaukaurally1–3, activity (Fig. 2a and Supplementary Fig. 1). For each odorant, we Jonathan Beroud1,2 & Alan Carleton1,2 analyzed the image sequence (Online Methods and Supplementary Fig. 2) and quantified the number of activated glomeruli (Fig. 2b In mammals, odorant molecules are thought to activate and Supplementary Fig. 3). We found that the number of activated only a few glomeruli, leading to the hypothesis that odor glomeruli for each stimulus ranged between 10 and 40 glomeruli representation in the olfactory bulb is sparse. However, the (Fig. 2b). For the same set of 30 natural stimuli, the total number of studies supporting this model used anesthetized animals or activated glomeruli per olfactory bulb was 443 ± 15 glomeruli (n = 5 monomolecular odorants at limited concentration ranges. mice; Fig. 2c,d). By merging the glomeruli activated by several odor- Using optical imaging and two-photon microscopy, we found ants (Online Methods), we obtained a map composed of glomeruli that natural odorants at their native concentrations could elicit with a unique identity showing that the natural odorants that we dense representations in the olfactory bulb. -
Functional Organization of Sensory Input to the Olfactory Bulb Glomerulus Analyzed by Two-Photon Calcium Imaging
Functional organization of sensory input to the olfactory bulb glomerulus analyzed by two-photon calcium imaging Matt Wachowiak*, Winfried Denk†, and Rainer W. Friedrich†‡ *Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215; and †Department of Biomedical Optics, Max Planck Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved May 10, 2004 (received for review January 20, 2004) Glomeruli in the olfactory bulb are anatomically discrete modules OSNs distinguished by histochemical markers terminate in dis- receiving input from idiotypic olfactory sensory neurons. To ex- crete subregions of the axonal compartment (36, 37). These data amine the functional organization of sensory inputs to individual raise the possibility that functionally distinct subdivisions exist .glomeruli, we loaded olfactory sensory neurons with a Ca2؉ within a glomerulus indicator and measured odorant-evoked presynaptic Ca2؉ signals Direct measurements of the activity of glomerular afferents within single glomeruli by using two-photon microscopy in anaes- have been difficult because most functional measures of intra- thetized mice. Odorants evoked patterns of discrete Ca2؉ signals glomerular activity lack sufficient spatial resolution or cellular throughout the neuropil of a glomerulus. Across glomeruli, Ca2؉ specificity. Here, we loaded OSNs with a fluorescent Ca2ϩ signals occurred with equal probability in all glomerular regions. indicator and measured patterns of afferent presynaptic activity ؉ Within single glomeruli, the pattern of intraglomerular Ca2 sig- within glomeruli by two-photon Ca2ϩ imaging in anaesthetized nals was indistinguishable for stimuli of different duration, iden- mice. Our data indicate that OSN input to individual glomeruli tity, and concentration. -
Medial Temporal Lobe (The Limbic System)
MEDIAL TEMPORAL LOBE (THE LIMBIC SYSTEM) On the medial surface of the temporal lobe are three structures critical for normal human functioning. From rostral to caudal, they are the olfactory cortex, the amygdala, and the hippocampus. We will look at the anatomy and function of each separately, although they are often grouped together as "the limbic system". A. The olfactory system: The olfactory system actually begins in the roof of the nasal cavity. The olfactory receptors are ciliated epithelial cells with an array of receptors capable of detecting thousands of different odors. However, just as with any sensory system, the receptor neurons themselves do not project to the cerebral hemispheres. Their axons project up through the cribiform plate of the skull to synapse on the dendrites of the mitral cells of the olfactory bulb. The axons of the olfactory receptors make up the elusive cranial nerve I. This fragile tract is susceptible to shearing forces in head trauma, and loss of smell is a surprisingly debilitating injury. Here is an example of a section through olfactory bulb. The olfactory bulb is not a simple relay (something which passively transmits the signal), but is a sophisticated structure in itself. The mitral cell- olfactory neuron synapse is actually within a tangle of axons and dendrites that is called a glomerulus. There is a second cell type tucked around these glomeruli which probably affects how the signal is transmitted. These cells are small and densely packed, which gives them the name "granule cells". However, they bear no relation to the granule cells of the cerebellum or cerebral cortex. -
Histology and Surface Morphology of the Olfactory Epithelium in the Freshwater Teleost Clupisoma Garua (Hamilton, 1822)
FISHERIES & AQUATIC LIFE (2019) 27: 122 - 129 Archives of Polish Fisheries DOI 10.2478/aopf-2019-0014 RESEARCH ARTICLE Histology and surface morphology of the olfactory epithelium in the freshwater teleost Clupisoma garua (Hamilton, 1822) Saroj Kumar Ghosh Received – 07 May 2019/Accepted – 27 August 2019. Published online: 30 September 2019; ©Inland Fisheries Institute in Olsztyn, Poland Citation: Ghosh S.K. 2019 – Histology and surface morphology of the olfactory epithelium in the freshwater teleost Clupisoma garua (Hamil- ton, 1822) – Fish. Aquat. Life 27: 122-129. Abstract. The anatomical structure of the olfactory organ and Introduction the organization of various cells lining the olfactory mucosa of Clupisoma garua (Siluriformes; Schilbeidae) were The olfactory system in fishes is a notable sensory or- investigated with light and scanning electron microscopy. The olfactory organ was composed of numerous lamellae of gan because it is essentially a chemoreceptor for de- various sizes, radiating outward from both sides of the narrow tecting and identifying water-soluble compounds to midline raphe, forming an elongated rosette. Each lamella collect information about the surrounding aquatic consisted of the olfactory epithelium and a central lamellar ecosystem. Smell is one of the most significant space, the central core. The epithelium covering the surface of senses, and it drives basic patterns of behaviors in the rosette folds was differentiated into zones of sensory and most teleosts such as foraging, alarm response, pred- indifferent epithelia. The sensory part of epithelium was characterized by three types of morphologically distinct ator avoidance, social communication, reproductive receptor neurons: ciliated receptor cells, microvillous receptor activity, and homing migration (Gayoso et al. -
Taste and Smell Disorders in Clinical Neurology
TASTE AND SMELL DISORDERS IN CLINICAL NEUROLOGY OUTLINE A. Anatomy and Physiology of the Taste and Smell System B. Quantifying Chemosensory Disturbances C. Common Neurological and Medical Disorders causing Primary Smell Impairment with Secondary Loss of Food Flavors a. Post Traumatic Anosmia b. Medications (prescribed & over the counter) c. Alcohol Abuse d. Neurodegenerative Disorders e. Multiple Sclerosis f. Migraine g. Chronic Medical Disorders (liver and kidney disease, thyroid deficiency, Diabetes). D. Common Neurological and Medical Disorders Causing a Primary Taste disorder with usually Normal Olfactory Function. a. Medications (prescribed and over the counter), b. Toxins (smoking and Radiation Treatments) c. Chronic medical Disorders ( Liver and Kidney Disease, Hypothyroidism, GERD, Diabetes,) d. Neurological Disorders( Bell’s Palsy, Stroke, MS,) e. Intubation during an emergency or for general anesthesia. E. Abnormal Smells and Tastes (Dysosmia and Dysgeusia): Diagnosis and Treatment F. Morbidity of Smell and Taste Impairment. G. Treatment of Smell and Taste Impairment (Education, Counseling ,Changes in Food Preparation) H. Role of Smell Testing in the Diagnosis of Neurodegenerative Disorders 1 BACKGROUND Disorders of taste and smell play a very important role in many neurological conditions such as; head trauma, facial and trigeminal nerve impairment, and many neurodegenerative disorders such as Alzheimer’s, Parkinson Disorders, Lewy Body Disease and Frontal Temporal Dementia. Impaired smell and taste impairs quality of life such as loss of food enjoyment, weight loss or weight gain, decreased appetite and safety concerns such as inability to smell smoke, gas, spoiled food and one’s body odor. Dysosmia and Dysgeusia are very unpleasant disorders that often accompany smell and taste impairments. -
The Pattern of Olfactory Innervation by W
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.9.3.101 on 1 July 1946. Downloaded from THE PATTERN OF OLFACTORY INNERVATION BY W. E. LE GROS CLARK and R. T. TURNER WARWICK From the Department of Anatomy, University of Oxford (RECEIVED 31ST JULY, 1946) IT is desirable that, from time to time, commonly Methods accepted statements regarding anatomical pathways Most of the observations recorded in this paper were and connexions in the peripheral and central nervous made on rabbit material. The fixation of the olfactory systems should be carefully reviewed in the light of mucosa presented considerable difficulty. The method modern technical methods of investigation, for it finally selected, because it gave the best results with must be admitted that not a few of these statements protargol and was also adequate for the other stains are based on old methods which are now recognized employed, was perfusion of 70 per cent. alcohol through to be too crude to permit of really accurate con- the aorta, after preliminary washing through with normal clusions. In recent years, indeed, a number of saline, as recommended by Bodian (1936). Another facts have been shown unexpected difficulty arose from the fact that a large apparently well-established number of laboratory rabbits suffer from a chronic by critical studies to be erroneous. For example, rhinitis which leads to gross pathological changes in the the so-called ventral nucleus of the lateral geniculate olfactory mucosa. Consequently, a considerable pro- Protected by copyright. body and the pulvinar are no longer accepted as portion of our material, experimental and otherwise, terminal stations of the optic tract, and the strie had to be discarded as useless. -
Asymmetric Neurotransmitter Release Enables Rapid Odour Lateralization in Drosophila
SUPPLEMENTARY INFORMATION doi:10.1038/nature11747 SUPPLEMENTARY NOTES Note S1: Light offset produced a precise compensatory turn in the direction opposite to the light-evoked turn (Fig. 1g). As a result, the fly’s net lateral displacement after this compensatory turn was close to zero (Fig. 1i). A train of light pulses produced a larger turn, and the fly’s compensatory turn after light offset was commensurately larger, although less precise (Fig. 1i). This suggests that the fly keeps track of how far it has turned away from its original path, and the accuracy of its estimate depends on how far it has strayed. Note S2: Resting GCaMP fluorescence (F) was not significantly different in the right and left glomeruli (p = 0.67, n = 6, paired t-test). This is expected because each glomerulus contains the axons arising from both the right and left antennae. Although one antenna is removed, the cut axons arising from that antenna are still present in the neuropil. Thus, both right and left glomeruli must contain the same number of GCaMP molecules, and so resting fluorescence is the same. Spontaneous ORN activity evidently makes little contribution to F. What is the mechanistic basis for the significant ipsi/contra difference in F/F? A previous study reported that an ORN plasma membrane marker is two-fold more abundant in the ipsilateral glomerulus as compared to the contralateral glomerulus1. This suggests that the ipsilateral arbor is simply larger than the contralateral arbor of the same ORN. If the properties of ipsi- and contralateral branches are the same, then the ipsi/contra asymmetry in F/F should be roughly proportional to the ipsi/contra asymmetry in arbor size. -
Olfactory Bulb Glomeruli: External Tufted Cells Intrinsically Burst at Theta Frequency and Are Entrained by Patterned Olfactory Input
1190 • The Journal of Neuroscience, February 4, 2004 • 24(5):1190–1199 Cellular/Molecular Olfactory Bulb Glomeruli: External Tufted Cells Intrinsically Burst at Theta Frequency and Are Entrained by Patterned Olfactory Input Abdallah Hayar, Sergei Karnup, Michael T. Shipley, and Matthew Ennis Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland, Baltimore, Maryland 21201 Glomeruli, the initial sites of synaptic processing in the olfactory system, contain at least three types of neurons collectively referred to as juxtaglomerular (JG) neurons. The role of JG neurons in odor processing is poorly understood. We investigated the morphology, spon- taneous, and sensory-evoked activity of one class of JG neurons, external tufted (ET) cells, using whole-cell patch-clamp and extracellular recordings in rat olfactory bulb slices. ET cells have extensive dendrites that ramify within a single glomerulus or, rarely, in two adjacent glomeruli. All ET neurons exhibit spontaneous rhythmic bursts of action potentials (ϳ1–8 bursts/sec). Bursting is intrinsically gener- ated; bursting persisted and became more regular in the presence of ionotropic glutamate and GABA receptor antagonists. Burst fre- quency is voltage dependent; frequency increased at membrane potentials depolarized relative to rest and decreased during membrane potential hyperpolarization. Spontaneous bursting persisted in blockers of calcium channels that eliminated low-threshold calcium spikes (LTS) in ET cells. ET cells have a persistent sodium current available at membrane potentials that generate spontaneous bursting. Internal perfusion with a fast sodium channel blocker eliminated spontaneous bursting but did not block the LTS. These results suggest that persistent sodium channels are essential for spontaneous burst generation in ET cells. -
Smell and Stress Response in the Brain: Review of the Connection Between Chemistry and Neuropharmacology
molecules Review Smell and Stress Response in the Brain: Review of the Connection between Chemistry and Neuropharmacology Yoshinori Masuo 1,*, Tadaaki Satou 2 , Hiroaki Takemoto 3 and Kazuo Koike 3 1 Laboratory of Neuroscience, Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan 2 Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; [email protected] 3 Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan; [email protected] (H.T.); [email protected] (K.K.) * Correspondence: [email protected]; Tel.: +81-47-472-5257 Abstract: The stress response in the brain is not fully understood, although stress is one of the risk factors for developing mental disorders. On the other hand, the stimulation of the olfactory system can influence stress levels, and a certain smell has been empirically known to have a stress- suppressing effect, indeed. In this review, we first outline what stress is and previous studies on stress-responsive biomarkers (stress markers) in the brain. Subsequently, we confirm the olfactory system and review previous studies on the relationship between smell and stress response by species, such as humans, rats, and mice. Numerous studies demonstrated the stress-suppressing effects of aroma. There are also investigations showing the effects of odor that induce stress in experimental animals. In addition, we introduce recent studies on the effects of aroma of coffee beans and essential oils, such as lavender, cypress, α-pinene, and thyme linalool on the behavior and the expression of stress marker candidates in the brain. -
The Olfactory Bulb As an Independent Developmental Domain
Cell Death and Differentiation (2002) 9, 1279 ± 1286 ã 2002 Nature Publishing Group All rights reserved 1350-9047/02 $25.00 www.nature.com/cdd Review The olfactory bulb as an independent developmental domain LLo pez-Mascaraque*,1,3 and F de Castro2,3 established. Does it awake the developmental program of the cells at the site being innervated or, does their arrival simply 1 Instituto Cajal-C.S.I.C., Madrid, Spain serve to refine the later steps of the developmental program? 2 Hospital RamoÂn y Cajal, Madrid, Spain In order to address this question, much attention has been 3 Both authors contributed equally to this work focused on the sophisticated development of the mammalian * Corresponding author: L LoÂpez-Mascaraque, Instituto Cajal, CSIC, Avenida del cerebral cortex where two different theories have been Doctor Arce 37, 28002 Madrid, Spain. Tel: 915854708; Fax: 915854754; E-mail: [email protected] proposed to explain the mechanisms underlying its formation. In the `protomap' model, cortical regions are patterned prior to Received 13.2.02; revised 30.4.02; accepted 7.5.02 the migration of the newborn neurons (intrinsic control),1 an Edited by G Melino event presumably specified by important molecular determi- nants.2 In this model, the arrival of innervating axons would Abstract merely serve to modify and refine the protomap (an important The olfactory system is a good model to study the facet of maintenance). In the second model, the `protocortex' theory, the newborn cortical neurons are a homogeneous cell mechanisms underlying guidance of growing axons to their population, that later on in corticogenesis are patterned into appropriate targets. -
Neuropilin-1 Facilitates SARS-Cov-2 Cell Entry and Provides a Possible Pathway Into the Central Nervous System
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.07.137802; this version posted June 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system Ludovico Cantuti-Castelvetri1,2*, Ravi Ojha3*, Liliana D. Pedro 1,2*, Minou Djannatian1,2*, Jonas Franz4*, Suvi Kuivanen5*, Katri Kallio3, Tuğberk Kaya1,2,6, Maria Anastasina3,7, Teemu Smura5, Lev Levanov5, Leonora Szirovicza5, Allan Tobi8, Hannimari Kallio-Kokko9, Pamela Österlund10, Merja Joensuu11, Frédéric A. Meunier11, Sarah Butcher3,7, Martin Sebastian Winkler12, Brit Mollenhauer13, Ari Helenius14, Ozgun Gokce6,19, Tambet Teesalu3,15,16, Jussi Hepojoki5,17, Olli Vapalahti5,9,18, Christine Stadelmann4, Giuseppe Balistreri3§, Mikael Simons1,2,19§ 1Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany 2German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 3Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland 4 Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany 5University of Helsinki, Medicum, Department of Virology, Helsinki, Finland 6 Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany 7Helsinki Institute of Life Sciences-Institute of Biotechnology, University of Helsinki, Finland 8Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia 9University of Helsinki and Helsinki University Hospital, Department of Virology, Helsinki, Finland 10Department of Health Security, Finnish Institute for Health and Welfare (THL), Helsinki, Finland 11Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.