The sense of smell

Outline

Main Olfactory System

Odor Detection

Odor Coding

Accessory Olfactory System

Pheromone Detection

Pheromone Coding

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Human experiment: How well do we taste without smell?

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Brief Anatomy of the Olfactory System

mucus

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Olfactory neurons respond to odors

Cineole Isoamyl Acetate Acetophenone

Firestein et al., J Physiol. 1993

neuron 1

neuron 2

neuron 3

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Models for Olfactory recognition

A. Vibrations of odor particles cause neurons to resonate at different frequencies

B. One receptor recognizes all odors with different affinities

C. One receptor recognizes a few odors; many different receptors to sense the different smells

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Olfactory Receptors are G Protein Coupled Receptors (GPCRs)

• largest family of receptors• hydrophobic/ hydrophilic

domains• seven transmembrane regions• Ligand-binding domain in plane

of membrane (TM3,5,6)• G protein binding domain in

loop 3 (btwn TM 5 and 6)

and C-terminus

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Humans have about 370 odorant receptorsMice have about 1000

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Each olfactory neuron contains one receptor

1. Each receptor is in 0.1% of cells2. Ten receptors are in 1% of cells3. Isolated olfactory neuron makes mRNA for only one receptor

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How is olfactory information mapped in the bulb?

Receptor map (labeled lines) Complex map (mixed lines)

In the Nose:Neurons express one receptorNeurons with the same receptor are in random locations

Topographic map?Odorant receptor map?Complex map?

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Neurons with the same receptor (blue) send axons to the same place

Epithelium to bulb Bulb cross-section

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Neurons with same receptor send axons to one glomerulus

Neurons with different receptors project to different glomeruli

The olfactory system uses labeled linesMap of odor receptors!!!

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• Fruit flies have 60 different receptors• Neurons with the same receptor project to one glomerulus

Glomerular structure is a general feature of olfactory systems

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Epithelium

Bulb

Basic Feature of Coding in the Olfactory Bulb

Olfactory neurons express 1 out of 1000 receptors

Neurons with the same receptorconverge on single glomeruliin olfactory bulb.

The glomeruli serve as modules, and are selectivelysensitive to particular odors

Model: Different odors activate different brain regions13

Response of Olfactory Bulbs to an Odorant Molecule, withthe Use of a Voltage Sensitive Dye.

Technologies: calcium-sensitive dyes, voltage-sensitive dyes and intrinsic signals (changes in blood flow, oxygen levels)

Results:•Odors activate a few glomeruli•Same glomeruli activated on repeated exposure•Different odors activate different glomeruli

Is there a map of different smells in the brain?

Rat olfactory bulb, olfactory imaging

Raw data C6 odor 2 times C3 odor then C6 odor

Plan: monitor neural activation in the brain

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How does an olfactory neuron choose only one receptor?

How do neurons find the right glomerulus?

How are odors processed by the brain?

Open questions in olfaction

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The receptor is involved in axon guidance

Schematics of the olfactory bulbReplace one receptor with another, targeting changes

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Signal Transduction in the Olfactory Epithelium

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Cellular Structure of Olfactory Bulbs

Lateral Olfactory Tract

Glomeruli

Olfactory Nerve

Periglomerular Cells

Granule Cells

Mitral/Tufted Cells

Receptor Cells

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Central Pathways of the Olfactory System

1. Olfactory sensory neurons project directly to the brain

2. From the olfactory bulb, information is sent to five different brain regions

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People sniff when they imagine pleasant odors

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Accessory Olfactory System

The Second Nose: the Vomeronasal organ

• detects pheromones (chemical cues secreted by animals)

• best evidence of pheromones in insects, many mammals

• triggers stereotyped behaviors (mating and fighting)

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The two noses in a mouse

(vomeronasal organ)22

How does the How does the VNO sense pheromones?

• Two large families of receptors (GPCRS)

• Not related to olfactory receptors

• Logic similar: one receptor per cell

• Projections different: neurons with same receptor project to many little glomeruli

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Anatomy in the Vomeronasal System

One receptor per neuronNeurons with same receptor project to many “glomeruli”

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Signal Transduction in the Vomeronasal System

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What happens to mice when their VNO doesn’t work?

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Do humans sense pheromones thru the VNO?

• There is a VNO• There is not an Accessory Olfactory Bulb• TRP channel is a pseudogene• VNO receptors are pseudogenes

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Main points about the olfactory system

1) Lots of receptors

2) One receptor per cell

3) Labeled lines in the olfactory bulb

4) Maps of different smells

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