14 Olfaction 2012-1


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  • Important for quality of life
  • Involves both taste and smell
  • Olfaction and the Limbic System Regions in our brain that are associated with memory and emotion
  • Some people can detect up to 100,000 different odorants
  • 1% of our genome
  • A naive animal responds behaviorally to the presence of pheromones without any prior experience or exposure:
  • Mice unidentified chemicals in male urine can induce estrous in female mice
  • Unidentified chemical cues (blue icons) in the C57B/6 male urine induce estrus in the Balb/C female. (B) After mating of the C57B/6 stud male to the Balb/C female, she forms a memory to the stud male ’s urinary peptides (yellow icons), inhibiting the estrus-inducing effect of his own chemical pheromones and ensuring successful pregnancy (left). (i). If the pregnant Balb/C female is subsequently exposed to a male of a different strain as the mating male (Balb/C), his urinary peptide profile (green icons) is not recognized by the female, and his chemical cues induce estrus resulting in termination of the original pregnancy (ii) MHC peptides are sufficient for this effect since, after mating to C57B/6 male, the female can be induced to return to estrus simply by exposure to C57B/6 urine spiked with BALB/c peptides .
  • Most mammals
  • compounds collected from the armpit and dabbed under the nose have the same effect on women. A woman's compounds collected during one part of the menstrual cycle will shorten another female's cycle an average of 1.7 days. Compounds from another part of the cycle will lengthen another female's cycle an average of 1.4 days. This indicates that two pheromones exist.
  • 14 Olfaction 2012-1

    1. 1. -receptor cells are neurons-long distance-chemesthesis refers to ability to detect irritating stimuli-vomeronasal requires contact w/stimuli; important for mammals, butnot for primates Chemoreception Nasal Oral Chemoreception Chemoreception (Smell) (Taste) Olfaction Chemesthesis Gustation Chemesthesis (Trigeminal Chemoreception) (Trigeminal Chemoreception) Vomeronasal Chemoreception Introductory Neurobiology 2012
    2. 2. Olfaction,The Common Chemical Sense and Vomeronasal Chemoreception Introductory Neurobiology 2012
    3. 3. -nasal cavity is where we sense odors -two routes: sniffing directly through the nose or through the nasal cavityIntroductory Neurobiology 2012
    4. 4. Chemosensory Systems in Mammalian Nose: •Main Olfactory -general odorants •Accessory Olfactory (Vomeronasal) -pheromones •Trigeminal (Chemisthesis) -irritating/pungent volatiles Introductory Neurobiology 2012Rodriguez. Nat. Neuro.(2003)
    5. 5. -pheromones are instinctual, butnot entirely-detecting predators, aggressivedisplays, maternal behavior,finding mates, provides directinput to amygdala Introductory Neurobiology 2012
    6. 6. Olfaction (Smell)-hyposmia: reduced sense of smell-anosmia: no sense of smell; can have a generalor specific (lose ability to smell specific odors)-cacosmia: having olfactory hallucinations[smelling things that arent there] Introductory Neurobiology 2012
    7. 7. The Importance of Olfaction Introductory Neurobiology 2012
    8. 8. Our Sense of SmellCan really influence and alter ourmoodCan influence how long we stay in aroomSharpens our awareness of otherpeople places and things.Can influence who we talk to andwho we want to talk again (ifhistocompatability group is different,better chance of bonding) Introductory Neurobiology 2012
    9. 9. Early warning system Introductory Neurobiology 2012
    10. 10. “The Dogtor is in” (Pet Scans) -sense odor from body Moles-melanoma Breast cancer Lung cancer Introductory Neurobiology 2012
    11. 11. Specificity and intensity of dog responses to breath/urine 99% accurate vs biopsies! Introductory Neurobiology 2012
    12. 12. Flavorretronasal smell-majority of flavor is smell, predominantly-olfactory bulb in human is less than size of pinky nail Bitter Sweet Sour Salty Umami (MSG) Introductory Neurobiology 2012
    13. 13. Emotions Memories-olfactory memories are very strong-Several branches of olfactory nerve going to olfactory bulb-olfactory bulb provides direct input to the amygdala; alsoinvolves memory Introductory Neurobiology 2012
    14. 14. Odor and MemoriesRecallVision: 50% accurate after only 3monthsSmell: 65% accurate after a year Introductory Neurobiology 2012
    15. 15. Structure of the Nose Introductory Neurobiology 2012
    16. 16. Introductory Neurobiology 2012
    17. 17. -crib inform plate separates nasal cavity from brain; olfactory nervesterminate in olfactory epithelium-receptor cells are neurons-first synapse is in the brain; in olfactory bulb-neurons terminate in cilia Introductory Neurobiology 2012
    18. 18. The Olfactory EpitheliumThe nose is the gateway to the brain(problem if wacked in nose, can get braininfections; diseases by amebas get intonerve and go to brain)Potential risks of trauma to the nose Introductory Neurobiology 2012
    19. 19. -cilia is where initial events insensory transduction take place Introductory Neurobiology 2012 Linda Buck
    20. 20. -plate is very thin bone-neurons can regenerate, but there is a lot of scar tissue that can prevent neuronsfrom going back to place Introductory Neurobiology 2012
    21. 21. -first synapse is in olfactory bulb-neurons will go to glomerulus-there is a specificity in glomeruli Introductory Neurobiology 2012
    22. 22. -pathway is from OE to OBto OC-sense of smell goesthrough cortex then thethalamus Introductory Neurobiology 2012 Linda Buck
    23. 23. Transduction Mechanisms in Mammalian Nose -g-protein is Golf -cAMP will open ion channel that allows Na and Ca to come in -Ca will open Cl channel to leave neuron to further depolarize -same tranduction pathways for smells, difference in receptor -~300 different receptors Introductory Neurobiology 2012Rodriguez. Nat. Neuro.(2003)
    24. 24. The Olfactory Receptor Neuron Introductory Neurobiology 2012
    25. 25. From: S. Ramon y Cajal y J.F. Tello y Muñoz. 1931Introductory Neurobiology 2012
    26. 26. -when we stimulate neuron, we generate receptor potential -if receptor potential is sufficient, it will generate APIntroductory Neurobiology 2012
    27. 27. How many different odors can Humans discriminate?A.~ 300B.~ 1, 000C.~ 10, 000D.~ 1 million Introductory Neurobiology 2012
    28. 28. Common Odors Introductory Neurobiology 2012
    29. 29. Introductory Neurobiology 2012
    30. 30. Mechanisms ofOlfactory Transduction Introductory Neurobiology 2012
    31. 31. -each olfactory receptor expresses only one of the receptors Introductory Neurobiology 2012
    32. 32. Olfactory Coding Glomeruli Introductory Neurobiology 2012
    33. 33. -there is coding by glomeruli -all same receptor cells send their axons to the same glomeruli -individual receptors tend to go to individual glomeruliIntroductory Neurobiology 2012
    34. 34. -receptor 1 responds to moer than one odor but respond to differnt intensity -coding is combination of labeled-line and cross fiber codingIntroductory Neurobiology 2012
    35. 35. Olfactory Receptor Genes• Approximately 1000 genes in rodents• Each olfactory receptor neuron expresses only 1 olfactory receptor• These same receptors are expressed in the testis on sperm cells Introductory Neurobiology 2012
    36. 36. Nobel Prize in Physiology or Medicine 2004 Protein must be able to detect a large number of odorants One gene, multiple combinations (like immunity) A large family of genes each encoding a different receptorRICHARD AXEL LINDA BUCK Discovered the Odorant Receptor Gene family (in 1991) Introductory Neurobiology 2012
    37. 37. HUGE gene family Receptor Odorant Genes Large fraction of our genome Scattered throughout all of our chromosomes Each odorant gene codes for a protein that is sensitive to a particular chemical structure(s)• combinattion of receptors (1625) Introductory Neurobiology 2012
    38. 38. -how single glomerulus receives axons from neurons expressing one receptor -one receptor one glomerulusIntroductory Neurobiology 2012
    39. 39. -similar receptors are not distributed randomly, located in zones -specificity of zonation for olfactory receptor neuronsIntroductory Neurobiology 2012
    40. 40. Introductory Neurobiology 2012 Linda Buck
    41. 41. -olfactory epithelium is like a mosaic of differentreceptor neurons expressing different individualreceptors Linda Buck Introductory Neurobiology 2012
    42. 42. Mori K. et al. Science (1999)* ~ 1000 OR types* One OR type per cell* Subset of OR types per zone* Zone to Zone projection* Cells of the same type project to a small number of fields (glomeruli)* Different odors activate different fields Introductory Neurobiology 2012
    43. 43. -shows convergence Linda Buck Introductory Neurobiology 2012
    44. 44. -shows zone in olfactoryepithelium and axonsprojecting to differentglomeruli Linda Buck Introductory Neurobiology 2012
    45. 45. -4 receptor and odorants -multitude of combinations are possible -w/300 different receptors and 1000 different odors Linda BuckIntroductory Neurobiology 2012
    46. 46. -combinatorial coding is superimpozed on zonal label line coding Introductory Neurobiology 2012 Linda Buck
    47. 47. The Common Chemical Sense (Chemisthesis) The importance of the common chemical sense Introductory Neurobiology 2012
    48. 48. The Common Chemical Sense (Chemisthesis) Receptors Introductory Neurobiology 2012
    49. 49. -receptors for CCS are neurons; primarysensory neurons-form synapses in spinal cord Introductory Neurobiology 2012
    50. 50. -trigeminal nerve is the fifth cranial nerve -burning sensationIntroductory Neurobiology 2012
    51. 51. The Common Chemical Sense (Chemisthesis) Mechanism of transduction: Activation of TRP channels Introductory Neurobiology 2012
    52. 52. Trigeminal Chemoreception TRP channels are located directly on trigeminal nerve Heat measured in Scovill units Introductory Neurobiology 2012
    53. 53. Introductory Neurobiology 2012
    54. 54. Capsaicin desensitization Trigeminal Ganglion Peripheral Nerve Peripheral Terminal To Brain Stem Eye, Nose,-if acute stimulation, nerveACUTE TREATMENT or Mouthis stimulted-if chronic, nerve willbecome desensitized-if neonateal, nerve can bekilled and not recover CHRONIC TREATMENT vanillyl aclyamide alkyl chain NEONATAL Neurobiology 2012 Introductory TREATMENT
    55. 55. Figure 3 VR1 responds to purified vanilloids and pepper extracts.. c, Responses to capsaicin (10 M) and extracts derived from four varieties of peppers in oocytes expressing VR1 (30 s application). Bottom right, relative potencies of each pepper extract are plotted (mean s.e.m., n = 3). Values were normalized in each cell to responses obtained with capsaicin (10 M). Extracts evoked no responses in water- injected cells. Reported pungencies for pepper varieties (in Scoville units) are: Habanero (H), 100,000–300,000; Thai green (T), 50,000– 100,000; wax (W), 5,000–10,000; and Poblano verde (P), 1,000– 1,500 (ref. 23). Capsaicin (C) is rated as 16x106 units.From Caterina et al., Nature 389, 816 - 824 (23 Oct 1997) Introductory Neurobiology 2012
    56. 56. Relative “burn” of some common peppers• Bell pepper 0• Jalapeño 2,000 - 5,000 units• Serrano 5,000 - 15,000 units• Thai 50,000 - 100,000 units• Habañero 100,000 - 300,000 units• Ghost pepper 1-3 million units!!! Introductory Neurobiology 2012
    57. 57. Introductory Neurobiology 2012
    58. 58. Vanilloid receptor 1 (VR1) (TRPV1) Vanilloid-like receptor 1 (VRL-1)(TRPV2) Introductory Neurobiology 2012
    59. 59. -ligand-gated channel -capsaicin is fat- soluble -makes receptor open up at room temperatureIntroductory Neurobiology 2012
    60. 60. Cool Receptors (TRPM8) Introductory Neurobiology 2012
    61. 61. -TRPM8 responds to cold and mentholIntroductory Neurobiology 2012
    62. 62. TRPA1• Mustard oil∀ ∆9-tetrahydrocannibinol• Cinnamaldehyde Introductory Neurobiology 2012
    63. 63. Introductory Neurobiology 2012
    64. 64. Stimulation of Nasal Trigeminal Fibers• Associated with painful or irritating chemicals (tingling, stinging, burning)• Examples of physiological reflexes – decreased respiration – increased nasal secretion – closure of nares and glottis – sneezing• Effects of noxious stimulus is minimized and the individual is protected from further exposure Introductory Neurobiology 2012
    65. 65. Vomeronasal Chemoreception and Pheromones Introductory Neurobiology 2012
    66. 66. Pheromones Definition: any chemical or set of chemicals produced by a living organism that transmits a message to other members of the same species. Naive response, not learned e.g. pups suckle, males fight, and estrus cycles are altered. Their precise nature remains somewhat controversial• males have more whisker growth Introductory Neurobiology 2012
    67. 67. Invertebrate PheromonesFirst discovered insilkworm mothsFemales secrete aspecific blend ofodorants that is highlyattractive to malesmales fly upwind tofind the source (as faraway as a mile away) Introductory Neurobiology 2012
    68. 68. Vertebrate PheromonesSwabbed Hamster A male hamster swabbed with hamster pheromone (“Aphrodisin”) became sexually attractive to another male hamster Introductory Neurobiology 2012
    69. 69. Bruce EffectMale Urine can induceestrus (heat)Bruce effect = odormemory Same mouse: pregnancy maintained New mouse or urine spike with pheromone: pregnancy terminated Introductory Neurobiology 2012
    70. 70. The Importance of theVomeronasal Organ (VNO) and Pheromones Mating behavior Territorial behavior Other conspecific behavior Introductory Neurobiology 2012
    71. 71. -VNO is located in pit in base of nose-goes to accessory olfactory bulb-projects to medial amygdala Introductory Neurobiology 2012
    72. 72. Vomeronasal OrganSecondary OlfactorySystem Sensory neurons synapse onto an Accessory Olfactory BulbMouse: at base of nasal cavity responds to bodily fluids introduced into the cavity (non-volatile)The Pheromone detector? MOB detects pheromones as well– terminate in microvilli Introductory Neurobiology 2012
    73. 73. Mating BehaviorAnecdote about male hamster Androstenone Introductory Neurobiology 2012
    74. 74. Introductory Neurobiology 2012
    75. 75. Behaviors Mediated by Vomeronasal Organ and Main Olfactory Epithelium From Mombaerts•Aggressive behavior •Discrimination of•Mating partner preference general odors (instrumental•Vocalizations conditioning, habituation/•Endocrine effects (e.g. puberty dishabituation?) delay, synchronization of estrous) Introductory Neurobiology 2012
    76. 76. Introductory Neurobiology 2012
    77. 77. Human Pheromones?Anecdotal: man’s whisker growth faster inthe presence of womenWomen who live together tend to get theirperiod during the same time of the month.Chemicals collected from the armpit anddabbed under the nose have the same effecton women One chemical will shorten the menstrual cycle by 1.7 days Another chemical will lengthen the cycle by 1.4 days Introductory Neurobiology 2012
    78. 78. MHCMajor Histocompatibility Complex Identified as a major component in tissue graft rejectionAlso appears to influence our body odorMechanism for detecting people withsimilar (or different) genotypes? Introductory Neurobiology 2012
    79. 79. Human VNO?Human fetus have a VNO but connections appear to disappear after ~19 weeks of ageAdult: usually a depression (or pit) in nasal cavity not always there or on both sides most human VNO Receptors are pseudogenes... Introductory Neurobiology 2012
    80. 80. “When, from a long-distant past nothing remains,After the people are dead;after the things are broken and scattered.Still, alone, more fragile,but with more vitality,more insubstantial,but more persistent, more faithful,the smell and taste of things remain poised forever,like ghosts, ready to remind us… Remembrance of Things Past ––––Marcel Proust Introductory Neurobiology 2012