The sense of smell Outline Main Olfactory System

The sense of smell Outline Main Olfactory System Odor Detection Odor Coding Accessory Olfactory System Pheromone Detection Pheromone Coding 1

Human experiment: How well do we taste without smell? 2

Brief Anatomy of the Olfactory System mucus 4

Olfactory neurons respond to odors Cineole Isoamyl Acetate Acetophenone neuron 1 neuron 2 neuron 3 5 Firestein et al. , J Physiol. 1993

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 (TM 3, 5, 6) • G protein binding domain in loop 3 (btwn TM 5 and 6) and C-terminus 6

Humans have about 370 odorant receptors Mice have about 1000 7

Each olfactory neuron contains one receptor 1. Each receptor is in 0. 1% of cells 2. Ten receptors are in 1% of cells 3. Isolated olfactory neuron makes m. RNA for only one receptor 8

In the Nose: Neurons express one receptor Neurons with the same receptor are in random locations How is olfactory information mapped in the bulb? Topographic map? Odorant receptor map? Complex map? Receptor map (labeled lines) Complex map (mixed lines) 9

Neurons with the same receptor (blue) send axons to the same place Epithelium to bulb Bulb cross-section 10

Neurons with same receptor send axons to one glomerulus Neurons with different receptors project to different glomeruli The olfactory system uses labeled lines Map of odor receptors!!! 11

Glomerular structure is a general feature of olfactory systems • Fruit flies have 60 different receptors • Neurons with the same receptor project to one glomerulus 12

Basic Feature of Coding in the Olfactory Bulb Olfactory neurons express 1 out of 1000 receptors Neurons with the same receptor converge on single glomeruli in olfactory bulb. The glomeruli serve as modules, and are selectively sensitive to particular odors Epithelium Model: Different odors activate different brain regions 13

Is there a map of different smells in the brain? Plan: monitor neural activation in the brain 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 Raw data C 6 odor 2 times C 3 odor then C 6 odor Response of Olfactory Bulbs to an Odorant Molecule, with the Use of a Voltage Sensitive Dye. Rat olfactory bulb, olfactory imaging 14

Open questions in olfaction How does an olfactory neuron choose only one receptor? How do neurons find the right glomerulus? How are odors processed by the brain? 15

The receptor is involved in axon guidance Expt: Replace one M 72 receptor with M 71, targets to M 71 glomerulus A. M 71 promoter-M 71 receptor-GFP B. M 71 promoter- M 71 receptor--RFP C. co-label A B C D. M 71 promoter-M 71 receptor-GFP E. M 72 promoter- M 72 receptor--RFP F. co-label D E F M 71 promoter-M 71 receptor-GFP M 72 promoter- M 71 receptor--RFP G. co-label G Replace one receptor with another, targeting changes 16

Signal Transduction in the Olfactory Epithelium 17

Cellular Structure of Olfactory Bulbs Receptor Cells Olfactory Nerve Glomeruli Periglomerular Cells Mitral/Tufted Cells Granule Cells Lateral Olfactory Tract 18

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 19

People sniff when they imagine pleasant odors 20

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) 21

The two noses in a mouse (vomeronasal organ) 22

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 23

Anatomy in the Vomeronasal System One receptor per neuron Neurons with same receptor project to many “glomeruli” 24

Signal Transduction in the Vomeronasal System 25

What happens to mice when their VNO doesn’t work? 26

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 27

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 28