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Les sens chimiques

Prof. Alan Carleton

Département de Neurosciences Fondamentales

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• Le système olfactif principal

• Organe voméronasal et détection des phéromones

• La perception des goûts

Les sens chimiques

(3)

GUSTATION

(4)

Organisation anatomique de la perception du goût

(5)

Les bourgeons du goût et papilles gustatives

(6)

Organisation des bourgeons du goût

20 µm

Bourgeons du goût:

Homme (10000) Rat (1000)

500 CV

(7)

Amer

Caffeine

Quinine-HCl

Atropine

Denatonium

Sucré

Fructose

Sucrose

Artificial Sweeteners

Umami

MSG

Salé

NaCl

KCl

Acide

Nicotinic Acid

Tartaric Acid HCl

Citric Acid

Les saveurs du goût

(8)

Bitter Sweet Umami

40 T2Rs T1R2/T1R3 T1R1/T1R3 Salt Sour

Ion channels GPCRs

ENAC

Epithelial Na Chan. Pkd2l1

Les receptors du goût

(9)

Transduction

ATP 5-HT

T1R2-T1R3 T1R1-T1R3 ENAC

Epithelial Na Chan.

PKD2L1

TRP channel

(10)

Transduction

(11)

Representation sensorielle sur la langue

(12)

Gustatoray pathways in the human brain

(13)

Gustatoray pathways in the rodent brain

(14)

Gilbertson et al. J Neurosci (2001)

Codage de l’information sensorielle

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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

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Location of the gustatory cortex in the rodent brain

mca

rhv S1BF

GC

S1

Pir lot

GC rs IC

(19)

• Changes in Reflectance upon activation

• Functional Population Activity

• Successfully used to establish spatial organization of other sensory areas

• Good Spatial Resolution

Methods – Intrinsic imaging

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Functional localization of the gustatory cortex

Accolla, Bathellier, Petersen and Carleton. Journal of Neuroscience (2007) 27:1396-1404

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Signals are taste specific

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Represention des goûts dans le cortex

Control C T A Extinction

C

B

Pleasant Unpleasant

A

Sweet Salty Bitter Sour

mca

rhv

Somatosenrory

(23)

Gustotopic map in the taste cortex

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Gustotopic map in the taste cortex

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OLFACTION

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Organization of the human olfactory system

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Organization of the olfactory systems

Photo: courtesy of Prof. Rodriguez (UNIGE)

(Omp-TauLacZ) Tg mouse Grueneberg

Ganglion (GG)

Vomeronasal

Organ (VNO) Main olfactory

Epithelium (MOE)

Olfactory

Bulb (OB)

(28)

Grueneberg ganglion

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Grueneberg ganglion

(30)

Chemical senses receptors

(31)

Vomeronasal receptors

(32)

Organization of the olfactory systems

V2R V1R

OR

(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, 1009-1014 (2007)

(36)

Organization of the olfactory system

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Organization of the main olfactory system

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Organization of the main olfactory system

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The main olfactory epithelium

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Sensory neurons in the main olfactory epithelium

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Sensory neurons in the main olfactory epithelium

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Organization of the main olfactory epithelium

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Transduction in the MOE

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Transduction in the MOE

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Transduction in the MOE

(46)

Organization of the olfactory system

The Nobel Prize in Physiology or Medicine 2004

L. Buck R. Axel

(M50-TauLacZ) Tg mouse

~1000 olfactory

receptors in mice

(47)

Zonal organization

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Simplex and complex odors

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Odor detection in mammals

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cyclohexanol CH 3

O

O

O O

CH 2 OH OH

O CH 3 O

O

anisole acétophenone

1,8 cinéole

dl- camphre

cyclodecanone

heptanol

cyclohexanone 2-heptanone

Sicard, G. and Holley, A. (1984). Receptor cell responses to odorants: similarities and differences among odorants. Brain Research, 292, (2), 283-96.

(51)

One receptor is not specific of a single molecule

Different odors are detected by different sets of receptors

Olfactory epithelium Sensory neuron

Chemodetection

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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

Ethyl Butyrate Amyl

acetate

(57)

Odor maps

Methyl Benzoate Water

Amylacetate Benzaldehyde

Hexanal

Carvone + (1) Carvone + (2)

(58)

Odor evoked glomeruli maps

A m yl ac et at eM e t h yl B e n z o at eB e n z al d eh yd eMouse C57Bl6- Odor maps from 03525510255010020051025501002005102550100200

Amylacetate

Methyl Benzoate

5 10 25 50 100 200

5 10 25 50 100 200

(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

Mouse

Human

(63)

Anosmia: loss of the sense of smell

Sensory neurons Mitral cells

(64)

Olfactory bulb circuitry

(65)

V es s el s

Odor Flow (sccm)

AA

EB

10

0.6 AA 0.4 EB

0.4 AA 0.6 EB

10

0.4

-0.5 0.5

-0.7

Frontal

Olfactory bulb

Medial

Spatial patterns of odor mixtures measured by intrinsic Imaging are highly similar in trained mice

Abraham et al. (2004). Neuron. 44:865-76

G lom er ul i

∆R/R

(66)

Behavioural assessment of olfactory performances

Abraham et al. (2004). Neuron. 44:865-76

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Mice can discriminate odors in a single sniff

1% AA vs. EB

Correct (%

40 100

80

60

40

13 1

Trials (block of 100) Cineol vs. eugenol

0.6AA+04EB vs.

0.4AA+0.6EB

Correct response (%)

Abraham et al. (2004). Neuron. 44:865-76

500 400 300 200 100

0

1%AA

1%EB Mix

D iscri mi n a ti o n t ime (ms) *

(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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