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O
N
O
jasmine
camphor
O
O
OH
O
O
O
apple
N
O
chocolate
lemon
O
O
O
musk
HO
HO
O
raspberry
vanilla
peppermint
Me
O
H
H
Me
O
amber
O
hyacinth
NH2
eucalyptus
SH
garlic
fish
O
grapefruit
O
O
N
H
O
H
fatty
N
O
marigold
H
OMe
Me
skunk
H
urine
SH
green pepper
woody
PEAR
O
O
BANANA
O
O
THE OLFACTORY SYSTEM AND INSTINCTIVE BEHAVIORS
N
HS
AGGRESSION
O
O
OH
PHEROMONES
O
N
O
MATERNAL BEHAVIOR
N
SEXUAL BEHAVIOR
N
S
PREDATOR ODORS
FEAR
THE OLFACTORY PATHWAY
Olfactory
Olfactory
Bulb
Bulb
(OB)
Olfactory
Epithelium
(OE)
Olfactory
Olfactory
cortex
Cortex
(OC)
THE VOMERONASAL PATHWAY
Accessory
Olfactory
Bulb
Vomeronasal
Organ
(VNO)
Medial
Amygdala
THE OLFACTORY EPITHELIUM
CILIA
STRUCTURE
mucus
cilia
supporting
cell
B. Menco, 1997
olfactory
sensory
neuron
basal stem
cell
axons
to olfactory bulb
THE SEARCH FOR ORs: combinatorial PCR
PCR PRODUCTS
PCR PRODUCTS + RESTRICTION ENZYME
TEN OLFACTORY RECEPTORS
THE
NOVEL MOTIFS IN OLFACTORY RECEPTORS
THE
hypervariable residues
OR GENES: EXPRESSION IN OLFACTORY EPITHELIUM
(OE)
OR GENES: A MULTIGENE FAMILY
THE OR GENE FAMILY IN HUMAN AND MOUSE
Human
Mouse
Total OR genes
638
1209
Intact OR genes
363
910
Pseudogenes
275
299
43
25
% pseudogenes
CHROMOSOMAL LOCATIONS OF HUMAN OR GENES
CANDIDATE PHEROMONE RECEPTORS IN THE
VOMERONASAL ORGAN
V1Rs
(~120)
V2Rs
(~140)
PATTERNS OF OR GENE EXPRESSION
IN OLFACTORY EPITHELIUM
OR-K20
OR-K21
OR-L45
OR-A16
Zone 4
EXPRESSION ZONES IN THE OLFACTORY EPITHELIUM
*
* * *
*
*
*
*
* **
*
*
**
* *** **
*
OLFACTORY EPITHELIUM:
A MOSAIC OF NEURONS EXPRESSING DIFFERENT ORs
IDENTIFICATION OF ORs FOR SPECIFIC ODORANTS
single olfactory
sensory neurons
odorants
calcium
imaging
single cell
RT-PCR
cDNAs
OR
TEST ODORANTS
#carbon
atoms
carboxylic
Carboxylic
Acid s
acids
alcohols
Alcohol s
bromocarboxylic
Bromocarboxylic
acidsAcid s
O
4
C4
OH
C5
OH
OH
C6
Br
hexanoic acid
OH
OH
heptanoic acid
hepta nol
octanoic aci d
octano l
C9
OH
nona nol
nonan oic
OH
O
O
Br
bromoh eptan oic
acid
OH
HO
*
heptanedi oic acid
O
HO
OH
OH
O octanedioic acid
bromooctanoic a cid
O
OH
Br
bromono nanoic acid
O
OH
O
OH
*
O hexanedioic a cid
O
9
pentanedi oic acid
OH
Br
OH
O
HO
O
C8
*
O
bromohexa noic aci d
OH
butanedi oic acid
OH
HO
bromope ntanoic acid
O
8
OH
O
OH
C7
O
Br
hexanol
7
O
O
O
6
OH
bromobuty ric acid
OH
pentanoic acid
penta nol
HO
Br
O
5
O
O
OH
butanoic acid
buta nol *
dicarboxylic
Dicarboxylic
Acid
s
acids
O
OH
*
HO
O
nonanedio ic acid
OH
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
ODORANTS ARE DETECTED BY COMBINATIONS OF ORS
ODORANT
ODORANT RECEPTOR
COMBINATORIAL
CODING
COMBINATORIAL
RECEPTOR
CODES FOR ODORS
ODORANTS
RECEPTORS
RECEPTOR CODES AND PERCEPTION
ODORANT RECEPTOR
RECEPTOR CODES: THE EFFECT OF CONCENTRATION
ODORANT RECEPTOR
ODORANTS
OH
OH
O
rose
O
OH
sweaty
ODOR
O
O
OH
O
OH
PHEROMONES
OH
aggression
subordination
INSTINCTIVE
BEHAVIOR
THE OLFACTORY BULB
olfactory bulb
glomerulus
olfactory
epithelium
To olfactory
cortex
Mitral cell
AXONS OF NEURONS WITH THE SAME OR CONVERGE
IN OLFACTORY BULB
OR-SPECIFIC GLOMERULI IN THE OLFACTORY BULB
medial
olfactory bulb
M71
A16
M50
0.5
mm
lateral
olfactory bulb
A STEREOTYPED MAP OF OR INPUTS
IN THE OLFACTORY BULB
ODOR CODING IN OLFACTORY EPITHELIUM AND BULB
O
O
OH
OH
OH
OH
OH
OH
OE
OB
ROSE
RANCID
THE OLFACTORY CORTEX
Anterior
olfactory
nucleus
(AON)
Olfactory
tubercle
(OT)
Piriform
cortex
(PC)
Amygdala
(Amg)
Entorhinal
cortex
(EC)
HOW ARE OR INPUTS ORGANIZEED IN THE CORTEX?
BARLEY LECTIN: A GENETIC TRANSNEURONAL TRACER
Pomp
BL
PompBL mice
olfactory
epithelium
olfactory
bulb
olfactory
cortex
COEXPRESSION OF BL WITH A SINGLE OR GENE
M5iBL mice
M5
IRES
BL
M50iBL mice
gene
(zone 1)
M5
M5
M50
IRES
BL
M50 IRES
BL
(zone 4)
IRES
BL
BL
mRNA
protein
M50
BL
BL IN THE OLFACTORY EPITHELIUM AND OLFACTORY BULB
olfactory epithelium
M5iBL
M50iBL
olfactory bulb
olfactory bulb
relay neurons
BL IN OLFACTORY CORTEX
PompBL
3.11mm
M50iBL-#1
3.15mm
3.15mm
M50iBL-#2
3.15mm
CLUSTERS OF BL+ CORTICAL NEURONS
IN M5iBL AND M50iBL MICE
anterior piriform cortex
PompBL
M5iBL
M5iBL
M50iBL
M50iBL
M50iBL
CLUSTERS OF BL+ CORTICAL NEURONS
IN M5iBL AND M50iBL MICE
olfactory tubercle
posterior piriform cortex
lateral entorhinal cortex
M5iBL
M5iBL
M5iBL
M50iBL
M50iBL
M50iBL
A STEREOTYPED MAP OF OR INPUTS
IN OLFACTORY CORTEX
DIVERGENCE AND PARALLEL PROCESSING OF OR INPUTS
OE
OB
OC
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)
INPUTS FROM DIFFERENT ORS OVERLAP IN CORTEX
OE
OB
OC
INPUTS FROM DIFFERENT ORS ARE COMBINED
IN SINGLE CORTICAL NEURONS
OE
OB
OC
MODEL: CORTICAL NEURONS AS
COINCIDENCE DETECTORS
OH
O
O
OR1
OR2
OR3 OR4
ACKNOWLEDGMENTS
Kerry Ressler
Susan Sullivan
Hiroaki Matsunami
Bettina Malnic
Lisa Horowitz
Zhihua Zou
Jean-Pierre Montmayeur
Collaborators:
Takaaki Sato
Junzo Hirono