University of Connecticut Graduate School
MEDS 371: Systems Neuroscience
2011
Chemosensory Systems: Taste
Marion E. Frank, Ph.D.
Professor
Center for Chemosensory Sciences
Oral Health & Diagnostic Sciences
School of Dental Medicine
GUSTATORY SYSTEM
Purpose of Taste—Detect Nutrients and Poisons
1 of 3 Chemical Senses, Taste---other Smell
and Chemesthesis—Chemical activation of Somesthesis
Cool of Menthol, Hot of Capsaicin
1 Chemical may activate all 3 senses, e.g. Ethanol
Chemicals that Taste: Water Soluble
Quality to
Humans,
[Also Good-Bad,
Post-Ingestional]
TASTE QUALITIES
SOUR
acetic acid
citric acid
HCl
SWEET
sucrose
fructose
saccharin
SALTY
NaCl
KCl
Na2SO4
NH4Cl
UMAMI: MSG
BITTER
quinineHCl
MgSO4
caffeine
Taste Tetrahedron
5 NEW TASTES
1. 2 NEW CARBOHYDRATE: MALTODEXTRIN & STARCH
2. FATS: FREE FATTY ACIDS, eg. CAPROIC, LINOLEIC
3. CALCIUM SPECIFIC
4. WATER
Taste Criteria
a. Logical purpose
b. Defined stimulus class
c. Transduction mechanism
d. Gustatory system involvement
e. Unique perception
f. Behavioral/physiological effect.
Taste Coding Logic according to Charles Zuker
Taste stimuli
2. Taste
1. Taste
receptors
cells
activated
3. Signals
Taste bud
relayed to
taste nerve
4. Taste nerve transmits
Signals to brain.
From Yarmolinsky
DA, Zuker CS,
Ryba NJP. 2009.
Common sense
about taste: from
mammals to
insects. Cell 139:
234-244.
Pattern Coding---2 Ways
Non-specific
Receptor Cells
Non-specific
Nerve Fibers
Chorda tympani S Neuron: Responses to Sucrose
Sweet Rhythm---Temporal Coding?
20
.03 M Sucrose
15
10
5
0
20
.1 M Sucrose
Impulses / 100 ms
15
10
5
0
20
15
.3 M Sucrose
10
5
0
20
1.0 M Sucrose
15
10
5
0
-0.5
0.0
0.5
1.0
1.5
2.0
Time (Sec)
From Frank et al., 2005
2.5
3.0
3.5
Candidate Taste Receptors
GPCRs
Ion Channels
From Yamolinsky et al., 2009
2 Kinds of Initial Taste Transduction
 gustducin
GPCR and Ion-channel
[Zhao, Zhang, Hoon, Chandrashekar, Erlenbach, Ryba & Zucker; Cell, 2003]
Aspartame activates human but not mouse T1R2+3
1. Mouse with hT1R2+3 Receptor in Sweet Cells
aspartame
TR determines Chemical Selectivity.
RASSL = Receptor Activated Soley by Synthetic Ligand
2. Mouse with RASSL in Sweet Cells
opioid
TRC Activation determines Appetitive Behavior.
Carnivora
Viverridae
Mustelidae
Weasels
Carnivora
Canidae
Civets
Viverridae
Canis
Taste: Species
Variation
(Diversification)
Caniformia
Procyonidae
T1R in Carnivores
Feliformia
Racoons
Mustelidae
Ursidae
Felidae
Hyaenidae
Herpestidae
Cats
Bears
Otariidae
Carnivora
Mustelidae
Weasels
Cani
Mus
Caniform
Wea
Proc
Procyonidae
Procyonidae
Caniformia
Racoons
Sea lions
Hyenas
CaniformiaCaniformia
Carnivore
evolutionary
tree
Ursidae
Ursidae
Odobenidae
Bears
Walruses
Mongooses showing branching of
Raco
U
Otariidae
Feliform
Sea lions
Seals and Caniform
aboutOdobenidae
60 MYA. Odobenidae
SeaO
Otariidae
Phocidae
Viverridae
Canidae
CiveC
Civets
Bear
Walr
Walruses
Figure
1. An evolution
Canis
Phocidae 2002 an
2005,
Arnason
Figure 1. An evolutionary tree of the carnivores (redrawn based
on Flynn 2005, Nowak
Seal
Phocidae Feliformia and Canifor
2005, Arnason 2002 and Bininda-Emonds 1999 ). Two major branches ofSeals
Order Carnivora,
Mustelidae
different diet
ea
Weasels
Figure 1. An evolutionary
tree within
of the car
Canidae
Dish = Diet
Feliformia and Caniformia, were diverged approximately 60 MYA . The dish symbols show
2005,
Arnason 2002 and
Bininda-Emonds
Carnivore
= carnivore;
=
different diet within each family.
tree
ofCaniformia,
the carnivores
(redrawn
ba
Procyonidae Figure 1. An evolutionary
Feliformia
and
were
diverged
Racoons
Insectivore
Arnason
2002
and
Bininda-Emonds
1999
Two 2005,
major
= carnivore; Figure
= omnivore;
= herbivore;
=
piscivore;
= insectivore.
1. 2005,
An evolutionary
tree
of the
carnivores
(redrawn
based
on).Flynn
No
different
diet within
each
family.
Feliformia
and
Caniformia,
were
diverged
approximately
60
2005, Arnason 2002 and Bininda-Emonds
1999
).
Two
major
branches
of
Order
Ca
Caniformia
=Omnivore
carnivore;
= omnivore;
=h
Ursidae different diet within each
family.
Bears
Feliformia
and Caniformia,
were diverged
approximately 60 MYA . The dish symbo
different diet within
each family. =Herbivore
= carnivore;
omnivore;
= herbivore;
= pis
Otariidae
= carnivore;Sea lions
= omnivore;
Odobenidae
Phocidae
Walruses
Piscivore
= herbivore;
= piscivore;
From Li, X.
Seals
Pseudogenization: Cats no T1R2 (sweet taste) (Li et al, 2006)
and Pandas (Carnivora) no T1R1 (glutamate taste) (Zhao et al, 2010).
Figure 1. An evolutionary tree of the carnivores (redrawn based on Flynn 2005, Nowak
2005, Arnason 2002 and Bininda-Emonds 1999 ). Two major branches of Order Carnivora,
Feliformia and Caniformia, were diverged approximately 60 MYA . The dish symbols show
different diet within each family.
= carnivore;
= omnivore;
= herbivore;
= piscivore;
= insectivore.
= insectiv
Species Differences:
Bitter to Humans: Ionic or Non-ionic
CH2 CH
H
Ionic
HO
Sensitivity
differences
H
N
H H
CH3O
CH3
O
C2H5
NHCCH2N CH2
C2H5
Cl
CH3
N
Denatonium Benzoate
Quinine Hydrochloride
Non-Ionic
CH2OAc
O H AcOCH2
O
H
H
H
OAc H
H AcO
O
AcO
CH2OAc
H
OAc
C6H5COO
Human
Qui: 10M
Dntn: 10nM
SOA: 7M
Caff: 3mM
OAc
H
O
Sucrose Octaacetate (SOA) (Ac = CH3C )
O
CH3
O
CH3
N
N
N
CH3
N
Caffeine
Taste the same to humans
Hamster
Qui: 0.3mM
Dntn: 1mM
SOA: 1mM
Caff: 3mM
Species Differences: 2 “Bitters” in Hamsters
Conditioned Taste Aversion
100
25
A
SO
af
C
M
A
SO
C
M
D
af
-50
gS
-50
en
-25
ui
-25
gS
0
en
0
50
ui
25
75
Q
% SUPPRESSION
50
Q
% SUPPRESSION
75
30 mM Caffeine
D
1 mM Quinine HCl
100
CS: Conditioned stimuli
CS: Qui = 1 mM QuinineHCl, Den = 3 mM Denatonium benzoate.
MgS = 180 mM MgSO4, Caf = 100 mM Caffeine,
SOA = 1.5 mM Sucrose octa-acetate. From Frank et al., 2004.
Taste Bud
Taste Receptor
Cells
10-day Lifespan
Type I, II, III
Receptor cells
I: dark, glia-like
II: T1 & T2 Rs
III: synapse with
nerve.
Cell Types in Taste Bud
From Finger, 2005
Pannexin 1 hemichannels- ATP
From Chaudhari N, Roper
SD. 2010. The cell biology of
taste. J Cell Biol 190:285-296.
I. Type I cells degrade/absorb neurotransmitters and may clear extracellular K+ that
accumulates after action potentials (shown as bursts) in receptor and presynaptic cells.
II. Receptor cell. Taste compounds induce release of ATP through pannexin1 (Panx1)
hemichannels. The extracellular ATP excites ATP receptors (P2X, P2Y) on sensory nerve
fibers and on taste cells. Presynaptic cells, in turn, release serotonin (5-HT), which inhibits
receptor cells.
III. Presynaptic cell. Sour stimuli directly activate presynaptic cells. Only
presynaptic cells form ultrastructurally identifiable synapses with nerves.
Distribution of Taste Buds in Mouse Oral Cavity
From Yamolinsky et al., 2009
Diagram of Rat Tongue
cv
fn
fo
fn : fungiform, fo : foliate, cv : circumvallate
3 Cranial Nerves areTaste Nerves
[Geniculate
ganglion]
[Glossopharyngeal]
[X n. to Pharynx]
Place taste buds are suggests function, CT easier to dissect than GL
Chorda Tympani Generalist and Specialist Neurons
CT = chorda tympani
Generalists
H neurons
Specialists
N neurons
S neurons
Activity
CT
nerve
N
E
Behavior
NaCl
CTA
Na+ K+ NH4+
N
E
+
Amiloride
Na+ K+ NH4+
Na+ K+ NH4+
+
Na+ K+ NH4+
Behavior
Na+ K+ NH4+
Activity
Amiloride block of ENaC changes taste of NaCl in rodents.
Na+ K+ NH4+
Rodent Na+ taste is more specific than human salty taste.
The GL does not use ENaC to detect Na+; CT and GSP do.
Rat Glossopharyngeal Nerve Recording
From Frank et al., 2008
Rodent Taste Pathways
Humans no
PbN relay
From Yamolinsky et al., 2009
Convergence of Taste Information on
Brainstem Neurons
CN VII
CT = chorda tympani nerve
GSP = greater superficial
petrosal nerve
NTS = n. solitary tract
P = palate
T = tongue
PT= : same stimulus
PT : different stimuli
Role of Inhibition? GABAergic and glycinergic inhibitory neurotransmitters in NTS
Human Central Taste Pathways
N. VII = facial nerve
N. IX = glossopharyngeal nerve
N. X = vagus nerve
Dealing with Natural Settings
A simple way to simulate natural tasting in humans.
Vary Timing and Concentration of Multiple Distinct Stimuli
A taste example.
4 Stimuli Presented in
Pairs: Adapt-Test.
• N = 100 mM NaCl
• S = 300 mM sucrose
• NS = Mix of N and S
• 0 = Water
•10 subjects identified
2 replicates of 16 test
stimuli after 5-sec
adaptation.
•Stimuli were “Taste
Puffs” to the tip of the
tongue.
Mixture Suppression and Selective Adaptation
Sucrose
NaCl
Selective Adapted Mixture
Sucrose
NaCl
Cross, Self & Mixture Adaptation
100
% Correct Identification
% Correct Identification
100
80
60
40
80
60
40
20
20
0
EXTRA
0
CROSS
SELF
MIXTURE
AMBIENT
ADAPTED
Test Stimulus Adapted State
Test Stimulus Adapted State
Characteristic tastes of sugar and salt) were readily
identified when preceded by water (dotted horizontal
lines) or after cross-adaptation but after self-adaptation
or mixture-adaptation tastes were less salient.
Within the binary mixture, the salt taste was less
identifiable than the sugar taste of sucrose [dotted
horizontal lines]. Sugar was just about perfectly identified
as a single, mixture or EXTRA component. The salt taste
was better identified as an EXTRA component after
adaptation to sucrose. As AMBIENT mixture
components, sugar and salt were even less salient than
self-adapted single components.
A way to study how the brain uses peripheral labeled lines?
Convergence of Sensory Inputs in Orbitofrontal Cortex
From Rolls, 2004
Gustatory System Summary
 We perceive sweet, salty, sour and bitter taste qualities.
 There are 3 types (I, II, III) of taste-bud receptor cells (TRC).
 TRC transduce chemicals in aqueous solution, using either GPCR: T1R for
sweet, T2R for bitter; or ion channels: TRP for sour, ENaC salty in rodents.
 TRC turn over and there is a neuron-taste bud neuro-trophism.
 Primary afferent neurons are specialists or generalists for taste quality.
Specialists are labeled lines sending specific quality information from the
receptors to the brain.
 CNS processing of taste information begins in the nucleus of the solitary tract
where neurons receive convergent input, show inhibition, and project to
VPMpc in the thalamus.
 Thalamic taste neurons project to primary taste cortex in anterior insula and
frontal operculum.
 Taste-quality discrimination and learning require thalamo-cortical pathways,
supplemented by pathways to amygdala and hypothalamus to add motivational
and hedonic features to tastes.
AN INTERESTING PAPER
Gulick D, Green AI. 2010. Role of caloric homeostasis and reward in
alcohol intake in Syrian golden hamsters Physiol Behav. 101: 518526.
Free-Access Drinking
WAT
ALC
SUC
WAT
ALC
WAT
Caloric Value
EXPERIMENT 1
Preference for alcohol or an ascending
sucrose concentration
14-day Baseline (2-bottles);
3rd bottle  Concentration every 5 days,
Measure 4 days, skipping 1st of 5.
WAT
ALC
Stimulus Compounds
CH2OH
O
H
H
OH
CH3CH2OH
H
HO
H
O
OH
Ethanol
O
H HOCH2
H
OH
O
H
HO
NH
CH2OH
SO2
H
Sucrose
Saccharin
STIMULUS COMPOUNDS
ETHANOL [v/v]
SUCROSE [mM]
SACCHARIN [ mM]
WATER
0
0
0
+
99
2
cal/g
228
4
357
6
485
8
15%
614
10
7
4
0
0
Ethanol and sucrose are metabolized for energy. 15% ethanol and 0.614 M
sucrose are equi-caloric. Saccharin is non-caloric;
4 mM saccharin and 614 mM sucrose are preferred by hamsters.
Ethanol caloric value is 7 calories, Sucrose 4 calories, Food 3.4 calories per gram.
ETHANOL INTAKE
W
W
A SU
A
W
A
W
Ethanol Intake falls as Sucrose concentration rises
in the 3rd bottle. Saccharin has no effect.
2-way ANOVA. Sucrose Concentration, Group and
Concentration by Group Interaction, all 3, p<0.001.
Decreased alcohol consumption with
sucrose but not saccharin shows hamster
alcohol consumption is tied to caloric content.
Suppression of alcohol intake by a sucrose
solution of lower caloric content supports a
role for reward value in alcohol consumption.
W
W
A
SA
W
A
W
A
 Results of our pilot study using conditioned taste aversions (CTA) suggests that
ethanol is not bitter but “SWEET” to golden hamsters. Generalizations from 10%
ethanol to 10 stimuli (TS) were tested with intake (mL) ratios for each ethanolconditioned animal to mean control intake for water-conditioned animals.
1.2
1.1
1.0
0.9
INTAKE RATIO
Test Stimuli
Water
5%,10%, 20% Ethanol
10% Isopropyl Alcohol
100 mM Sucrose
10 mM Vanillin
10 ppm Capsaicin
10 mM Caffeine
1 mM Quinine·HCl
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
The reward value of
sugar and ethanol may
evoke sweet signs for
calories in hamsters.
se
ter
ine
ine
illin
icin
OH
OH
OH
OH
W a % Et % Et % Et ropyl Sucro Van apsa Caffe Quin
0
0
5
p
C
1
2
Iso
STIMULUS
Ratios for alcohols, sucrose and capsaicin
fell beneath the ratio for control water.
The End