Saccharin sweet bitter tasteless Similar molecules – different taste

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Transcript Saccharin sweet bitter tasteless Similar molecules – different taste

The Sense of Taste
How tastes are detected by the tongue
How taste information is processed by the brain
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Function of Gustation
• Designed to detect picomolar (10-12) concentrations of
bitter substances
• Detects molar concentrations of nutritious substances
• Humans perceive sweet, sour, bitter, salty and umami
• Olfaction and taste collaborate in determining flavor.
• The somatosensory system establishes both localization
and texture.
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Organization of taste buds on the tongue
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Taste buds contain 50-100 taste cells
Taste cells are not neurons
Short lifetimes
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Similar molecules – different taste
Saccharin
O
O
O
O2 N
N
NH
CH3
NH
S
S
S
O
O
O
O
O
O
sweet
bitter
tasteless
Aspartame
O
O
H2N
OCH3
O
H2N
OCH3
N
H
sweet
OH
N
H
O
O
HO2
C
H2N
N
H
HO2C
O
HO2C
bitter
tasteless
Very different molecules are bitter
O
OH
H
O
O
O
N
H
H
H
OH
O
H
H
H
O
OH
OH
H
O
N
OH
O
O
O
OH
O
O
O
OH
OH
O
OH
Cucurbitacin B
Bitter thresholds:
1.8 nM
Amarogentin
Strychnine
0.6 mM
2 mM
Models of Taste Coding
Model A: Across-fiber patterning
Taste cells recognize multiple modalities;
brain must compare different cells activity to know what the mouth tastes
Model B: Labeled lines
Taste cells recognize one modality;
sweet cells fire and the brain perceives sweet
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Sweet taste
Mutant mouse cannot detect saccharin
Mutation is in a G protein coupled receptor
Two other receptors are nearby
T1R gene family = 3 genes
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T1R taste receptors localize to the taste pore
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Basic Techniques in Neurobiology
Identifying ligands for receptors
by calcium imaging
1. Put receptor gene + G15 into cells
G15
2. When receptor is activated by ligand,
Activates G15 leading to Ca increase
PLC—IP3 + DAG--- Ca release
3. Calcium dye changes fluorescence
T1R2 and T1R3 together recognize sugars
+ T1R2
+T1R3
+ T1R2 + T1R3
T1Rs are selectively co-expressed in taste cells
T1R1+3 &T1R3
T1R2+3
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Mice lacking T1R2 or T1R3 do not detect sugars
Expt: Give mice choice between water or water plus sugar
normal
mutant
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The T2Rs are a family of novel taste GPCRs
~30 receptors
found nearby genomic regions associated with bitter taste variations
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Most T2Rs are co-expressed in the same cells
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T2Rs function as receptors for bitter tastants
+ CYX
+ DEN
+ PROP
PROP
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There is no significant overlap between cells expressing
sweet, bitter and amino acid receptors
T1R3
T2Rs
T1Rs
T2Rs
Cross sections of a tongue labeled with receptor-specific antibodies
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Expression of T1Rs and T2Rs suggests that there are
bitter cells and sweet cells
Supports labeled line model of taste coding
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Many taste signaling cascades have been proposed
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T1Rs and T2Rs use a PLC-mediated cascade
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Are T1Rs and T2Rs in different cells?
Expt 1: knockout PLC--- mice can’t detect sweet or bitter
Expt 2: put PLC back in under control of one T2R promoter
what happens?
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Taste cells innervated by 3 nerves
facial (VII)
glossopharyngeal (IX)
vagus (X)
Solitary tract nucleus of medulla
hypothalamus, amygdala, gustatory cortex
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Taste in fruit flies to study neural circuits
• Taste with legs, wings, mouth
• 60 taste receptor genes not related to TRs
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Fly taste receptors are on legs, wings, mouth
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Does the taste system map position?
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Does the taste system map taste?
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Fly taste system maps
where the taste comes from (leg, mouth)
what taste category the neuron recognizes
(sweet, bitter)
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Main points about taste
• T1Rs recognize sugars
• T2Rs recognize bitter substances
•We recognize different modalities because
we have sugar cells, bitter cells, etc..
• Labeled line taste coding
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