SLIDE 1
SLIDE 2 raspberry
HO O
skunk
SH
fish
NH2
musk
O O O
fatty
O
camphor
OH
grapefruit
O
amber
O Me H Me H
hyacinth
O
marigold
O
chocolate
N N
garlic
SH
urine
O H H H
vanilla
O O
jasmine
O
eucalyptus
O
green pepper
N N O
peppermint
HO
woody
H Me OMe
apple
O O O O
lemon
O
SLIDE 3
O O
PEAR
O O
BANANA
SLIDE 4 THE OLFACTORY SYSTEM AND INSTINCTIVE BEHAVIORS
N S H
AGGRESSION
O O O OH
PHEROMONES N N MATERNAL BEHAVIOR
O
SEXUAL BEHAVIOR S N PREDATOR ODORS FEAR
SLIDE 5
THE OLFACTORY PATHWAY
Olfactory Epithelium (OE)
Olfactory Bulb Olfactory cortex
Olfactory Cortex (OC) Olfactory Bulb (OB)
SLIDE 6
THE VOMERONASAL PATHWAY
Vomeronasal Organ (VNO) Accessory Olfactory Bulb Medial Amygdala
SLIDE 7 THE OLFACTORY EPITHELIUM
CILIA STRUCTURE
sensory neuron supporting cell basal stem cell mucus cilia axons to olfactory bulb
SLIDE 8
THE SEARCH FOR ORs: combinatorial PCR
SLIDE 9
PCR PRODUCTS PCR PRODUCTS + RESTRICTION ENZYME
SLIDE 10
TEN OLFACTORY RECEPTORS THE
SLIDE 11
THE NOVEL MOTIFS IN OLFACTORY RECEPTORS
SLIDE 12 hypervariable residues
SLIDE 13
OR GENES: EXPRESSION IN OLFACTORY EPITHELIUM
(OE)
SLIDE 14
OR GENES: A MULTIGENE FAMILY
SLIDE 15
SLIDE 16
THE OR GENE FAMILY IN HUMAN AND MOUSE Human Mouse 638 1209 Total OR genes Intact OR genes 363 910 Pseudogenes 275 299 % pseudogenes 43 25
SLIDE 17
CHROMOSOMAL LOCATIONS OF HUMAN OR GENES
SLIDE 18
CANDIDATE PHEROMONE RECEPTORS IN THE VOMERONASAL ORGAN
V1Rs (~120) V2Rs (~140)
SLIDE 19
PATTERNS OF OR GENE EXPRESSION IN OLFACTORY EPITHELIUM
Zone 4
OR-K20 OR-K21 OR-L45 OR-A16
SLIDE 20 EXPRESSION ZONES IN THE OLFACTORY EPITHELIUM
* * * * * * * * * * * * * * * * * * * * * *
SLIDE 21
OLFACTORY EPITHELIUM: A MOSAIC OF NEURONS EXPRESSING DIFFERENT ORs
SLIDE 22 single olfactory sensory neurons
OR
cDNAs
IDENTIFICATION OF ORs FOR SPECIFIC ODORANTS
calcium imaging single cell RT-PCR
SLIDE 23 TEST ODORANTS
O OH pentanoic acid
OH
penta nol B r O
OH
bromope ntanoic acid
O H O O H O
pentanedi oic acid * O OH hexanoic acid
O H
hexanol
O Br OH
bromohexa noic acid
O H O O H O
hexanedioic a cid O OH heptanoic acid
OH
hepta nol O B r
O H
bromoheptanoic acid
*
O H O H O O
heptanedi oic acid O OH
O H
O Br O H
bromooctanoic a cid
O H O O H O
O OH nonanoic
O H
nona nol O Br
O H
bromononanoic acid *
O O H O O H
nonanedioic acid O OH butanoic acid
OH
buta nol * O B r
OH
bromobuty ric acid
O H O O H O
butanedi oic acid *
Alcohol s Carboxylic Acid s Bromocarboxylic Acid s Dicarboxylic Acid s
C4 C5 C6 C7 C8 C9
alcohols carboxylic acids bromocarboxylic acids dicarboxylic acids #carbon atoms 4 5 6 7 8 9
SLIDE 24 RESPONSES OF ONE NEURON TO ODORANTS
C 4 C 5 C 6 C 7 C 8 C 9 A 4 A 5 A 6 A 7 A 8 A 9 B 4 B 5 B 6 B 8 D 6 D 7 D 8 D 9
SLIDE 25
ODORANTS ARE DETECTED BY COMBINATIONS OF ORS
ODORANT RECEPTOR ODORANT
SLIDE 26
RECEPTORS ODORANTS
COMBINATORIAL CODING
COMBINATORIAL RECEPTOR CODES FOR ODORS
SLIDE 27
RECEPTOR CODES AND PERCEPTION
ODORANT RECEPTOR
SLIDE 28
RECEPTOR CODES: THE EFFECT OF CONCENTRATION
ODORANT RECEPTOR
SLIDE 29 O O
OH OH O OH OH O OH OH O
rose sweaty aggression subordination ODORANTS PHEROMONES ODOR INSTINCTIVE BEHAVIOR
SLIDE 30 THE OLFACTORY BULB
glomerulus
Mitral cell
epithelium
To olfactory cortex
SLIDE 31
AXONS OF NEURONS WITH THE SAME OR CONVERGE IN OLFACTORY BULB
SLIDE 32 OR-SPECIFIC GLOMERULI IN THE OLFACTORY BULB
M71 A16 M50 medial
lateral
0.5 mm
SLIDE 33
A STEREOTYPED MAP OF OR INPUTS IN THE OLFACTORY BULB
SLIDE 34 ODOR CODING IN OLFACTORY EPITHELIUM AND BULB
O OH
O OH OH
O H
OH OH
OE OB ROSE RANCID
SLIDE 35 THE OLFACTORY CORTEX
Anterior
nucleus (AON) Piriform cortex (PC) Olfactory tubercle (OT) Amygdala (Amg) Entorhinal cortex (EC)
SLIDE 36
HOW ARE OR INPUTS ORGANIZEED IN THE CORTEX?
SLIDE 37 BARLEY LECTIN: A GENETIC TRANSNEURONAL TRACER
BL Pomp
PompBL mice
epithelium
cortex
bulb
SLIDE 38 COEXPRESSION OF BL WITH A SINGLE OR GENE M5iBL mice M50iBL mice
IRES BL IRES BL gene
(zone 1) (zone 4)
M5 M50 M5 M50 IRES BL IRES BL mRNA BL M5 BL M50 protein
SLIDE 39 BL IN THE OLFACTORY EPITHELIUM AND OLFACTORY BULB
- lfactory epithelium
- lfactory bulb
- lfactory bulb
relay neurons
M5iBL M50iBL
SLIDE 40 BL IN OLFACTORY CORTEX
PompBL
3.15mm 3.11mm 3.15mm 3.15mm
M50iBL-#1 M50iBL-#2
SLIDE 41 CLUSTERS OF BL+ CORTICAL NEURONS IN M5iBL AND M50iBL MICE
anterior piriform cortex
PompBL M50iBL M5iBL M5iBL M50iBL M50iBL
SLIDE 42 CLUSTERS OF BL+ CORTICAL NEURONS IN M5iBL AND M50iBL MICE
M5iBL M5iBL M5iBL M50iBL M50iBL M50iBL
posterior piriform cortex lateral entorhinal cortex
SLIDE 43
A STEREOTYPED MAP OF OR INPUTS IN OLFACTORY CORTEX
SLIDE 44
DIVERGENCE AND PARALLEL PROCESSING OF OR INPUTS
OE OB OC
SLIDE 45
BL+ NEURONS IN ANTERIOR PIRIFORM CORTEX
PERCENT OF AREA OCCUPIED BY BL+ CLUSTERS M5iBL: 5.7% M50iBL: 4.2% NUMBER OF BL+ NEURONS PompBL: 179,570 ±3935 M50iBL: 4390 ±179 (2.4% of PompBL) M5iBL: 6570 ±217 (3.7% of PompBL)
SLIDE 46
INPUTS FROM DIFFERENT ORS OVERLAP IN CORTEX
OE OB OC
SLIDE 47
INPUTS FROM DIFFERENT ORS ARE COMBINED IN SINGLE CORTICAL NEURONS
OE OB OC
SLIDE 48 MODEL: CORTICAL NEURONS AS COINCIDENCE DETECTORS
OR1 OR3 OR2 OR4
O O OH
SLIDE 49
ACKNOWLEDGMENTS
Kerry Ressler Susan Sullivan Hiroaki Matsunami Bettina Malnic Lisa Horowitz Zhihua Zou Jean-Pierre Montmayeur Takaaki Sato Junzo Hirono Collaborators:
