LECTURE 18: OLFACTION AND TASTEREQUIRED READING: Kandel text, Chapter 32

Smell and Taste are the chemical senses

Smell (olfaction) is the discriminating sensation of volatile chemical odorants by theolfactory system

Taste is discriminating sensation of soluble chemicals by the gustatory system

Olfaction is far more discriminating than taste, and much of our subtle perceptualdistinctions 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, andis 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 intosubfamilies, 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. One olfactory neuron ----------------> One OR gene expressed

2. 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

The P2 OR gene was geneticallytagged with to coexpress a

Tau-GAL protein, which binds toaxon microtubules and is detected

With X-GAL.All axons converge to a single glomerulus

(from Wang et al, Cell 93:47;1998)

OBOE

Peppermint odor activatesa repertoire of odorantreceptors to stimulate a

distinct set of olfactory bulb glomeruli

(from Guthrie et al, PNAS 90:3329;1993)

All M50 OR-expressingaxons project toone glomerulus,

as detected by ISH

(from Ressler et al,Cell 79:1245;1994)

OLFACTORY INFORMATION IN GLOMERULI IS INTEGRATED ANDDISTRIBUTED TO DIFFERENT BRAIN CENTERS

PHEROMONES ARE SPECIES-SPECIFIC ODORANTS SENSED THROUGHA PARALLEL OLFACTORY SYSTEM

Specific pheromone receptorsexpressed in dispersedsensory neurons withinthe 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 areengineered to be expressed in cells thatwould normally express the P2 receptor,

the axons of these neurons project toa new glomerular “address”.

In P3 ---> P2 neurons, axons project towhere 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 adeterminant of axonal pathfinding,

it is NOT the only determinant.

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 areexposed to saliva through the taste pore

Tasty substance is sensed at microvilliby several mechanisms, but always

induces depolarization andaction potential generation

Taste cell action potential releasesneurotransmitter which activates

gustatory afferent fiber

Taste cells can detectone of five known tastes:

SOURSOURSALTYSALTYSWEETSWEETBITTERBITTERUMAMI

ORGANIZATION OF THE TASTE BUD

DIFFERENT TASTE STIMULI USE DIFFERENT SIGNAL TRANSDUCTION METHODS

SALTY-sensing taste cells expressamiloride-sensitive sodium channels.

Sodium in salts enters through channelto depolarize cell.

Potassium-type salts also stimulatethese cells because of leak potassium

channels and change in EK

SOUR-sensing taste cells expressproton-sensitive potassium

leak channels.

Acid H+ ions (protons) blockthese potassium channels,

reducing gK and depolarizing cell.

DIFFERENT TASTE STIMULI USE DIFFERENT SIGNAL TRANSDUCTION METHODS

SWEET-sensing taste cells use 7-TMreceptor coupled to Gs.

Sugars act through Gs to producecAMP, and PKA phosphorylates

and closes potassium leak channels,causing depolarization

Alternatively, some substances(artificial sweeteners) bind receptors

coupled to Gq which activatesPLC to increase Ca+2 through IP3

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 activatesPLC to increase Ca+2 through IP3

Other receptors couple to gustducin, whichactivates cyclic nucleotide phosphodiesterases

A few bitter compounds act by directly blockingleak potassium channels

TRANSMISSION OF TASTE INFORMATION TO THE BRAINAND PERCEPTION OF TASTE

Integration of taste stimuli first occurs in afferant gustatory fibers, since each fiber receives inputfrom 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.