SMELL 2

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1 SENSORY SYSTEMS 1

2 SMELL 2

3 TASTE 3

4 HEARING 4

5 TOUCH EQUILIBRIUM 5

6 PAIN 6

7 OTHER SENSES 7

8 HOW DO SENSORY CELLS CONVERT STIMULI INTO ACTION POTENTIALS? HOW DO SENSORY SYSTEMS DETECT CHEMICAL STIMULI? HOW DO SENSORY SYSTEMS DETECT MECHANICAL FORCES? 8

9 IONOTROPIC SENSORY RECEPTORS Sensory Cell Membrane Receptor Proteins Respond to Stimuli 9

10 METABOTROPIC SENSORY RECEPTORS Sensory Cell Membrane Receptor Proteins Respond to Stimuli 10

11 STIMULATING A SENSORY CELL PRODUCES A RECEPTOR POTENTIAL Receptor potential: generates action potentials in the receptor cell receptor potential action potentials 11

12 STIMULATING A SENSORY CELL PRODUCES A RECEPTOR POTENTIAL Receptor potential: generates action potentials in the receptor cell, or causes release of a neurotransmitter. receptor potential action potentials 12

13 CHEMORECEPTORS Chemoreceptors: receptor proteins that bind various ligands; responsible for TASTE and SMELL. Also monitor internal environment, such as CO 2 levels in blood. 13

14 CHEMORECEPTORS 7TM/G-PROTEIN ASSOCIATED RECEPTORS G-PROTEIN 14

15 THE THREE CHEMOSENSORY EPITHELIA IN THE MOUTH AND NOSE OF MAMMALS VNO: vomeronasal organ MOE: main olfactory epithelium 15

16 SMELL/ OLFACTION 16

17 OLFACTORY RECEPTORS COMMUNICATE DIRECTLY WITH THE BRAIN 17

18 OLFACTORY RECEPTORS COMMUNICATE DIRECTLY WITH THE BRAIN 18

19 OLFACTORY RECEPTORS COMMUNICATE DIRECTLY WITH THE LIMBIC SYSTEM basic physiological drives, instincts, and emotions (pleasure, pain, or rage) (fear) memory 19

20 ODORANT/OLFACTORY RECEPTOR SIGNALING 20

21 OLFACTORY RECEPTORS 21

22 OLFACTORY RECEPTORS 22

23 OLFACTORY RECEPTORS the odorant complementarity determining regions reside in the transmembranal segments 3, 4, and 5 OR Receptor Protein as viewed in the Swiss-PdbViewer with predicted odorant complimentary binding regions on helices 3,4 & 5 highlighted 23

24 OLFACTORY RECEPTOR GENES HUMAN: 906 OLFACTORY RECEPTOR GENES (>60% PSEUDOGENES). MOUSE: 1,296 OLFACTORY RECEPTOR GENES (20% PSEUDOGENES). 24

25 OLFACTORY RECEPTOR GENES Dark shade, receptors with known ligands. Light shade, receptors without identified ligands. GPCR, G-proteincoupled receptor; TR, taste receptor. 25

26 ODOR DISCRIMINATION A single olfactory neuron contains over a thousand receptor genes There is only a single enhancer capable of binding to the promoters of these genes and turning them on Only one olfactory receptor gene gets to be expressed in a single cell A mechanism for discriminating among a thousand or so odorants 26

27 ODOR DISCRIMINATION Each receptor is probably capable of binding to several different odorants some more tightly than others. Each odorant is capable of binding to several different receptors. This provides the basis for combinatorial diversity. Assume that Odorant A binds to receptors on neurons #3, #427, and #886. Odorant B binds to receptors on neurons #2, #427, and #743. The brain then would interpret the two different patterns of impulses as separate odors. A mechanism capable of discriminating among millions of different odorants. 27

28 THE TRIGEMINAL SENSE IN THE OLFACTORY EPITHELIUM 28

29 VOMERONASAL ORGAN 29

30 VOMERONASAL ORGAN 30

31 VOMERONASAL ORGAN 31

32 VOMERONASAL RECEPTORS a Odorant receptors and V1R vomeronasal receptors have short N- terminal extracellular domains, in contrast to V2Rs. The number of genes in each family is indicated in brackets. b The degree of amino acid conservation in the consensus sequence of an odorant receptor is represented as a colour in the rainbow spectrum, with blue being highly conserved and red highly variable. 32

33 VOMERONASAL RECEPTORS Phylogenetic tree of mouse V1R vomeronasal receptors. 33

34 VOMERONASAL ORGAN 34

35 TASTE GUSTATION 35

36 TASTE BUDS ARE CLUSTERS OF SENSORY CELLS 36

37 TASTE NOT TRUE 37

38 TASTE CONTRARY TO POPULAR BELIEF, THERE IS NO TONGUE 'MAP': RESPONSIVENESS TO THE FIVE BASIC MODALITIES BITTER, SOUR, SWEET, SALTY AND UMAMI IS PRESENT IN ALL AREAS OF THE 38 TONGUE.

39 receptor cells are tuned to respond to single taste modalities TASTE each sensory fiber innervates multiple taste buds, and within each taste bud, several taste cells 39

40 TASTE RECEPTORS T1R1+3: the umami receptor T1R2+3: sweet receptor T2Rs: bitter receptors PKD2L1: a candidate sour receptor PLC-2 is the effector of sweet, umami and bitter pathways TRPM5 the transduction channel40of sweet, umami and bitter pathways.

41 TASTE RECEPTORS Saltiness receptors are ionotropic 41

42 TASTE RECEPTORS 42

43 TASTE RECEPTORS 43

44 CHEMORECEPTORS, SUMMARY OLFACTORY RECEPTORS VOMERONASAL RECEPTORS TASTE RECEPTORS T1R3 T1Rs (3 genes) 44

45 MECHANORECEPTORS HEARING TOUCH 45

46 HEARING 46

47 STRUCTURES OF THE HUMAN EAR 47

48 STRUCTURES OF THE HUMAN EAR 48

49 STRUCTURES OF THE HUMAN EAR The cochlea is divided into compartments filled with fluids of distinct ionic composition. Perilymph is similar to extracellular fluid, but endolymph, which is found in the central compartment above the tops of the hair cells, contains a high 49 K+ concentration and a small amount of Ca2+.

50 STRUCTURES OF THE HUMAN EAR 50

51 SENSING PRESSURE WAVES IN THE INNER EAR 51

52 SENSING PRESSURE WAVES IN THE INNER EAR BÉKÉSY GYÖRGY The Nobel Prize in Physiology or Medicine

53 SENSING PRESSURE WAVES IN THE INNER EAR The area on the cochlea where the most hair cells are stimulated during a given sound wave is considered the resonance point, and loudness can be perceived by the number and duration of hair cell stimulation at that point. 53

54 54

55 HAIR CELLS STEREOCILIA HAIR CELL Hair Cells Have Mechanosensors on Their Stereocilia 55

56 HAIR CELLS STEREOCILIA HAIR CELL 56

57 HAIR CELLS HAVE MECHANOSENSORS ON THEIR STEREOCILIA 57

58 HAIR CELLS 58

59 HAIR CELLS 59

60 HAIR CELLS 60

61 HAIR CELLS 61

62 HAIR CELLS MET: mechanoelectrical transduction TRPA1: transient receptor potential channel A1 PMCA2a: plasma membrane CaATPase pump 62

63 INNER & OUTER HAIR CELLS INNER HAIR CELLS OUTER HAIR CELLS 63

64 INNER & OUTER HAIR CELLS 64

65 INNER & OUTER HAIR CELLS 65

66 INNER & OUTER HAIR CELLS Hair cells are the primary transducers of mechanical sound energy. The mammalian organ of Corti contains 2 sets of hair cells: OUTER HAIR CELLS, thought to be the amplifiers, INNER HAIR CELLS, thought to be the true sensory cell, sending frequency, amplitude, and timing information to the brainstem. Both cell types are stimulated by movement of the basilar membrane arising from pressure differences across the inner ear compartments. 66

67 OUTER HAIR CELLS Outer hair cells can generate force, mechanically boosting soundinduced vibrations of the hair bundle and augmenting frequency tuning. 67

68 BALANCE 68

69 ORGANS OF EQUILIBRIUM Mammalian inner ear has three SEMICIRCULAR CANALS at angles to each other; sense position and orientation of head. 69

70 ORGANS OF EQUILIBRIUM The VESTIBULAR APPARATUS has two chambers that sense position of head and acceleration. 70

71 THE LATERAL LINE ACOUSTIC SYSTEM 71

72 TOUCH 72

73 THE SKIN FEELS MANY SENSATIONS 73

74 STRETCH RECEPTORS 74

75 STRETCH RECEPTORS 75

76 PAIN 76

77 1. PAIN

78 1. PERIPHERAL NOCICEPTOR TERMINALS 78

79 1. PAIN RECEPTORS 79

80 2. PERIPHERAL NERVES M: myelinated U: unmyelinated 80

81 3. DORSAL ROOT GANGLION 81

82 4. SPINAL CHORD 82

83 4. SPINAL CHORD NK1: SUBSTANCE-P RECEPTOR AMPA: GLUTAMAT RECEPTOR 83

84 4. SPINAL CHORD 84

85 5. BRAIN 85

86 PAIN- SUMMARY 86

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