lalfabeto degli odori anna menini neurobiology sector international school for advanced studies...

95

Upload: hannah-pruitt

Post on 26-Mar-2015

218 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 2: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

L’alfabeto degli odori

Anna Menini

Neurobiology Sector

International School for Advanced Studies

Trieste, Italy

Page 3: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 4: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 5: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

XC N

cyanide

S HX

thiol

N H 2X

amine

B rX

Halides

Common Odor Compounds

formiates

XO Halcohols

C O O HX

carboxylic acids

X R

O

aldehydes

XO H

O

X H

O

ketones

estersX R

OR

Xalkanes

Page 6: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 7: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

What is a transduction process?

A transduction process is how the energy of an external

stimulus is converted into an electrical signal

Page 8: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Sensory cells convert a stimulus into an electrical response by a

process known as SENSORY TRANSDUCTION

Page 9: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

• 1- IONOTROPIC

2- METABOTROPIC

How many mechanisms of transduction?

C

l

RG

Na+ Ca2+

Ca2+Na

Lightmolecules

Page 10: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Receptor potential=Generator potential

• The change in membrane potential produced by the stimulus is a graded potential and can be:

• positive or depolarizing

• negative or hyperpolarizing

Page 11: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Sensory receptor cells

• Some sensory receptor cells have axons and generate action potentials

• Other cells do not generate action potentials

Page 12: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 13: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 14: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Scanning electron micrograph of the olfactory epithelium

E. Morrison and R. Costanzo

Page 15: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 16: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

1m

Morrison and Costanzo 1990

Page 17: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Olfactory transduction takes place in the cilia

Page 18: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 19: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

R

Page 20: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 21: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

R

Page 22: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 23: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 24: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 25: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 26: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 27: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

How many odorant receptor genes?

1,000 genes

Page 28: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Nobel Prize in Physiologyor Medicine 2004

• “for their discoveries of odorant receptors and the organization of the olfactory system”

Linda Buck

Richard Axel

Page 29: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

1000 recettori

350 recettori

Page 30: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

How many type of odorant receptor per cell?

1 type only

Page 31: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 32: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

How are odorant receptors spatially expressed in the

olfactory epithelium?

Randomly in each of four zones

Page 33: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 34: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 35: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 36: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

How many odorant molecules can activate an olfactory sensory

neuron ?

One neuron can respond to many odorant molecules

Page 37: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

One type of odorant molecule: how many types of odorant

receptors can activate?

One type of odorant molecule can activate many types of

odorant receptors

Page 38: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

PERA

BANANA

Page 39: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Denis

Page 40: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

A P B N O C D U G I R F P

DA IN

P U F

P O RD

B UA P

NA U

B N IC

Denis

Page 41: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 42: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

From olfactory epithelium to olfactory bulb

Representation of olfactory information

Page 43: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Mori et al., 1999

Zonal Organization in the Olfactory System

Page 44: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 45: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 46: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 47: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

GLOMERULI

Un certo odore attiva una definita combinazione di glomeruli

Page 48: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

NASO BULBO

Page 49: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Information coding in the olfactory cortex

Page 50: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 51: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 52: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

BulbEpithelium Cortex

Page 53: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

NASO BULBO CORTECCIA

Page 54: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Olfactory transduction cAMP is

the main second messenger

Page 55: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 56: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 57: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 58: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 59: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Ca concentration increases in the ciliaand has a dual effect

1- excitatory2- inhibitory

Page 60: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Ca excitatory effect:direct activation of Cl current

In situ Cl gradient measurements (rat, mucus/knob concentrations)

[Cl-]i = 69 mM[Cl-]o = 55 mM

Ecl = +6mV(Reuter et al.)

Page 61: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 62: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 63: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 64: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Adaptation

Page 65: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 66: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 67: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 68: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Adaptation

• Adaptation adjusts the dynamic range of the response to allow the sensory cell to respond to changes in odor concentration over a wide range.

Page 69: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Mechanism of adaptation

• Intracellular Calcium concentration controls adaptation acting on the transduction cascade

Page 70: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Transduction in an olfactory sensory neuron

Page 71: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 72: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Caged compound

Uncaged:physiologically active

Page 73: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 74: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 75: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 76: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 77: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 78: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 79: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 80: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 81: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 82: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 83: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 84: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 85: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

8-Bromo-cAMP

1- is resistant to hydrolysis by PDE

2- activates cAMP-gated channels with higher affinity than cAMP

Page 86: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 87: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 88: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 89: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 90: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 91: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 92: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy
Page 93: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Transduction in an olfactory sensory neuron

Page 94: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

S.I.S.S.A. Trieste

Page 95: Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies Trieste, Italy

Collaborators

C.N.R. GenovaCristiana PiccoPaola Gavazzo

S.I.S.S.A. TriesteLaura LagostenaAnna BoccaccioAndrea MazzatentaGiulietta PinatoSimone PifferiRanken Shimazaki

JapanTakashi Kurahashi

GermanyBenjamin Kaupp

USAStuart FiresteinPeter Mombaerts