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

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

4. Brief Anatomy of the Olfactory System mucus 4

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

6. 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 6

7. Humans have about 370 odorant receptors Mice have about 1000 7

8. 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 mRNA for only one receptor 8

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

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

11. 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

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

13. Epithelium Bulb 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 Model: Different odors activate different brain regions 13

14. Response of Olfactory Bulbs to an Odorant Molecule, with the 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 14

15. 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 15

16. The receptor is involved in axon guidance Replace one receptor with another, targeting changes 16 A. M71 promoter-M71receptor-GFP B. M71 promoter- M71 receptor--RFP C. co-label D. M71 promoter-M71receptor-GFP E. M72 promoter- M72 receptor--RFP F. co-label M71 promoter-M71receptor-GFP M72 promoter- M71 receptor--RFP G. co-label A B C D E F G Expt: Replace one M 72 receptor with M71, targets to M71 glomerulus

17. Signal Transduction in the Olfactory Epithelium 17

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

19. 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

20. People sniff when they imagine pleasant odors 20

21. 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

22. The two noses in a mouse (vomeronasal organ) 22

23. 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 23

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

25. Signal Transduction in the Vomeronasal System 25

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

27. 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

28. 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