Les sens chimiques Prof. Alan Carleton Département de Neurosciences Fondamentales

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1 Les sens chimiques Prof. Alan Carleton Département de Neurosciences Fondamentales

2 Les sens chimiques Le système olfactif principal Organe voméronasal et détection des phéromones La perception des goûts

3 GUSTATION

4 Organisation anatomique de la perception du goût

5 Les bourgeons du goût et papilles gustatives

6 Organisation des bourgeons du goût Bourgeons du goût: Homme (10000) Rat (1000) 500 CV 20 µm

7 Les saveurs du goût Salé Sucré Acide Amer Umami NaCl Fructose HCl Caffeine MSG KCl Citric Acid Sucrose Nicotinic Acid Quinine-HCl Artificial Sweeteners Tartaric Acid Atropine Denatonium

8 Les receptors du goût Bitter Sweet Umami GPCRs 40 T2Rs T1R2/T1R3 T1R1/T1R3 Salt Sour Ion channels ENAC Epithelial Na Chan. Pkd2l1

9 Transduction T1R2-T1R3 T1R1-T1R3 ENAC Epithelial Na Chan. PKD2L1 TRP channel ATP 5-HT

10 Transduction

11 Representation sensorielle sur la langue

12 Gustatoray pathways in the human brain

13 Gustatoray pathways in the rodent brain

14 Codage de l information sensorielle Gilbertson et al. J Neurosci (2001)

15 Codage de l information sensorielle Mouse behaviour Mueller et al. Nature (2005)

16 Codage de l information sensorielle Cortical neurons Stapleton et al. J Neurosci (2006)

17 Représentation sensorielle dans le cortex Vision Audition

18 Location of the gustatory cortex in the rodent brain S1BF mca S1 rhv GC IC Pir GC rs lot

19 Methods Intrinsic imaging Changes in Reflectance upon activation Functional Population Activity Good Spatial Resolution Successfully used to establish spatial organization of other sensory areas

20 Functional localization of the gustatory cortex Accolla, Bathellier, Petersen and Carleton. Journal of Neuroscience (2007) 27:

21 Signals are taste specific

22 Represention des goûts dans le cortex A mca B Somatosenrory Sweet Salty Bitter Sour C rhv Pleasant Unpleasant Control C T A Extinction

23 Gustotopic map in the taste cortex

24 Gustotopic map in the taste cortex

25 OLFACTION

26 Organization of the human olfactory system

27 Organization of the olfactory systems Grueneberg Ganglion (GG) Olfactory Bulb (OB) Vomeronasal Organ (VNO) Main olfactory Epithelium (MOE) (Omp-TauLacZ) Tg mouse Photo: courtesy of Prof. Rodriguez (UNIGE)

28 Grueneberg ganglion

29 Grueneberg ganglion

30 Chemical senses receptors

31 Vomeronasal receptors

32 Organization of the olfactory systems OR V2R V1R

33 Transduction in the VNO

34 Sexual behavior controlled by the vomeronasal organ

35 Sexual behavior controlled by the vomeronasal organ A functional circuit underlying male sexual behaviour in the female mouse brain Tali Kimchi, Jennings Xu & Catherine Dulac Nature 448, (2007)

36 Organization of the olfactory system

37 Organization of the main olfactory system

38 Organization of the main olfactory system

39 The main olfactory epithelium

40 Sensory neurons in the main olfactory epithelium

41 Sensory neurons in the main olfactory epithelium

42 Organization of the main olfactory epithelium

43 Transduction in the MOE

44 Transduction in the MOE

45 Transduction in the MOE

46 Organization of the olfactory system The Nobel Prize in Physiology or Medicine 2004 L. Buck R. Axel ~1000 olfactory receptors in mice (M50-TauLacZ) Tg mouse

47 Zonal organization

48 Simplex and complex odors

49 Odor detection in mammals

50 dl- camphre 1,8 cinéole cyclodecanone acétophenone CH 3 O O O O heptanol CH 2 OH OH cyclohexanol CH 3 O O 2-heptanone O cyclohexanone anisole Sicard, G. and Holley, A. (1984). Receptor cell responses to odorants: similarities and differences among odorants. Brain Research, 292, (2),

51 Chemodetection Sensory neuron One receptor is not specific of a single molecule Different odors are detected by different sets of receptors Olfactory epithelium

52 Odor coding = Combinatorial coding

53 Imaging odor maps Blood vessels pattern Functional Map

54 IOS imaging of odorant evoked activity in the olfcatory bulb

55 Functional organization of cortical regions

56 IOS imaging of odorant evoked activity in single trials Amyl acetate Ethyl Butyrate

57 Odor maps Water Methyl Benzoate Hexanal Amylacetate Benzaldehyde Carvone + (1) Carvone + (2)

58 Mouse C57Bl6- Odor maps from A m y l a c e t a t e M e t h y l B e n z o a t e B e n z a l d e h y d e Odor evoked glomeruli maps Amylacetate Methyl Benzoate

59 Olfactory mediated behavior

60 Organization of the olfactory system

61 Anosmia: loss of the sense of smell

62 Anosmia: loss of the sense of smell Human Mouse

63 Anosmia: loss of the sense of smell Sensory neurons Mitral cells

64 Olfactory bulb circuitry

65 Spatial patterns of odor mixtures measured by intrinsic Imaging are highly similar in trained mice Olfactory bulb Vessels AA EB 10 R/R Glomeruli Frontal Medial 0.6 AA 0.4 EB 0.4 AA 0.6 EB 10 Odor Flow (sccm) Abraham et al. (2004). Neuron. 44:865-76

66 Behavioural assessment of olfactory performances Abraham et al. (2004). Neuron. 44:865-76

67 Mice can discriminate odors in a single sniff Correct response (%) Cineol vs. eugenol Correct (% 13 Trials (block of 100) 1% AA vs. EB 0.6AA+04EB vs. 0.4AA+0.6EB Discrimination time (ms) %AA 1%EB * Mix Abraham et al. (2004). Neuron. 44:865-76

68 Olfactory bulb circuitry

69 Genetic manipulation of granule cell inhibition

70 Granule cell inhibition modulate odor discrimination More inhibition Less inhibition

71 Odor representation in the olfactory cortex Stettler and Richard Axel. Neuron (2009)

72 Odor representation in the olfactory cortex Stettler and Richard Axel. Neuron (2009)

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