Transcript LECTURE18.Olfaction&Taste

LECTURE 18: OLFACTION AND TASTE
REQUIRED READING: Kandel text, Chapter 32
Smell and Taste are the chemical senses
Smell (olfaction) is the discriminating sensation of volatile chemical odorants by the
olfactory system
Taste is discriminating sensation of soluble chemicals by the gustatory system
Olfaction is far more discriminating than taste, and much of our subtle perceptual
distinctions in flavors require integrating gustatory, olfactory & somatosensory information
ODORS ARE DETECTED BY NASAL OLFACTORY SENSORY NEURONS
Apical dendrite of sensory neuron projects through support cells to nasal cavity, and
is capped by dendritic cilia projecting into specialized mucus in the cavity
Olfactory sensory neurons are fairly short-lived (1-2 months), and regenerate from basal stem cells
Each sensory neuron responds to a single odorant or a specific repertoire of chemically related odorants
An odor is ENCODED by the specific combination of neurons which respond to it
Sensory neurons respond to odorant by inward current flow, which depolarizes neuron.
There is a relationship between odorant concentration and size/duration of inward current;
sufficient depolarization triggers action potential.
OLFACTORY SENSORY NEURONS EXPRESS ODORANT RECEPTORS
Clue to discovery of odorant receptors: Odors
trigger cAMP synthesis in
olfactory sensory neurons
Linda Buck and Richard Axel reasoned odorant
receptors were G-protein-coupled receptors
They searched for novel GPCRs expressed in subsets
of olfactory sensory neurons
using the techniques of reverse transcription +
polymerase chain reaction (RT-PCR)
combined with in situ hybridization (ISH)
Method led to discovery of
~1000 odorant receptor genes in mammals,
each encoding a 7-TM GPCR
Odorant receptors can be classified into
subfamilies, each having somewhat
greater amino acid sequence similarity
ODORANT RECEPTOR STIMULATION OPENS cAMP-GATED CATION CHANNEL
RULES OF ODORANT RECEPTOR GENE EXPRESSION
SOME RULES OF VERTEBRATE ODORANT RECEPTOR (OR) GENE EXPRESSION
ARE SIMILAR TO ANTIBODY GENE EXPRESSION
1.
2.
One olfactory neuron ----------------> One OR gene expressed
Allelic exclusion: Only one of two alleles of an OR gene expressed in a neuron;
Allelic choice is random
MORE RULES
1.
Each OR gene expressed in neurons interspersed within one of four domains of
nasal olfactory epithelium
2.
All axons from sensory neurons expressing the same receptor converge on
one or a few glomeruli within the olfactory bulb
THEREFORE, CELLS FOR DETECTING AN ODOR ARE DISPERSED IN EPITHELIUM,
AND ALL DETECTION OF THE ODOR IS GATHERED AND SUMMATED
INTO A SPECIFIC CLUSTER OF OLFACTORY BULB NEURONS
OR GENES EXPRESSED IN EACH OF FOUR SECTORS OF OLFACTORY EPITHELIUM
CONVERGENCE OF AXONS EXPRESSING A SPECIFIC ODORANT RECEPTOR
TO ONE OR A FEW GLOMERULI IN OLFACTORY BULB
OE
Peppermint odor activates
a repertoire of odorant
receptors to stimulate a
distinct set of olfactory bulb
glomeruli
(from Guthrie et al, PNAS
90:3329;1993)
All M50 OR-expressing
axons project to
one glomerulus,
as detected by ISH
(from Ressler et al,
Cell 79:1245;1994)
OB
The P2 OR gene was genetically
tagged with to coexpress a
Tau-bGAL protein, which binds to
axon microtubules and is detected
With X-GAL.
All axons converge to a single glomerulus
(from Wang et al, Cell 93:47;1998)
OLFACTORY INFORMATION IN GLOMERULI IS INTEGRATED AND
DISTRIBUTED TO DIFFERENT BRAIN CENTERS
PHEROMONES ARE SPECIES-SPECIFIC ODORANTS SENSED THROUGH
A PARALLEL OLFACTORY SYSTEM
Specific pheromone receptors
expressed in dispersed
sensory neurons within
the veromonasal organ
OLFACTORY RECEPTORS ARE USED TO GUIDE AXONS TO PROPER GLOMERULI:
OLFACTORY SENSORY AXONS LACKING ODORANT RECEPTOR WANDER AND DIE
(from Wang et al, Cell 93:47;1998)
OLFACTORY RECEPTORS ARE USED TO GUIDE AXONS TO PROPER GLOMERULI:
CHANGING ODORANT RECEPTOR EXPRESSED IN A NEURON CHANGES ITS PROJECTION
When different odorant receptors are
engineered to be expressed in cells that
would normally express the P2 receptor,
the axons of these neurons project to
a new glomerular “address”.
In P3 ---> P2 neurons, axons project to
where P3 neuron axons go.
But for other misexpressions, the
glomerular address is different from
both that of P2 or of the replacement OR.
Therefore, while the specific OR is a
determinant of axonal pathfinding,
it is NOT the only determinant.
ORGANIZATION OF THE TASTE BUD
Each taste bud contains ~100 taste cells
Mature taste cells are very short-lived,
and are continuously regenerated
from basal cells
Apical microvilli of taste cells are
exposed to saliva through the taste pore
Tasty substance is sensed at microvilli
by several mechanisms, but always
induces depolarization and
action potential generation
Taste cell action potential releases
neurotransmitter which activates
gustatory afferent fiber
Taste cells can detect
one of five known tastes:
SOUR
SALTY
SWEET
BITTER
UMAMI
DIFFERENT TASTE STIMULI USE DIFFERENT SIGNAL TRANSDUCTION METHODS
SALTY-sensing taste cells express
amiloride-sensitive sodium channels.
Sodium in salts enters through channel
to depolarize cell.
Potassium-type salts also stimulate
these cells because of leak potassium
channels and change in EK
SOUR-sensing taste cells express
proton-sensitive potassium
leak channels.
Acid H+ ions (protons) block
these potassium channels,
reducing gK and
depolarizing cell.
DIFFERENT TASTE STIMULI USE DIFFERENT SIGNAL TRANSDUCTION METHODS
BITTER-sensing taste cells use 7-TM receptors coupled to
various G proteins. Bitter sensation is method for recognizing
TOXIC compounds.
There is a family of related bitter receptors.
Some receptors couple to Gq which activates
PLC to increase Ca+2 through IP3
Other receptors couple to gustducin, which
activates cyclic nucleotide phosphodiesterases
A few bitter compounds act by directly blocking
leak potassium channels
SWEET-sensing taste cells use 7-TM
receptor coupled to Gs.
Sugars act through Gs to produce
cAMP, and PKA phosphorylates
and closes potassium leak channels,
causing depolarization
Alternatively, some substances
(artificial sweeteners) bind receptors
coupled to Gq which activates
PLC to increase Ca+2 through IP3
TRANSMISSION OF TASTE INFORMATION TO THE BRAIN
AND PERCEPTION OF TASTE
Integration of taste stimuli first occurs in afferant gustatory fibers, since each fiber receives input
from multiple taste cells of different types. Each gustatory afferent fiber has a response profile to 5 tastes
Taste stimuli project to the gustatory cortex, where it is consciously perceived.
Taste stimuli are integrated with somatosensory inputs to generate perception of where tasty substance is.
Taste perception is also shaped by parallel olfactory input;
the somatosensory stimulus “fools” us to perceive the olfaction as part of the taste.