1. Marion E. Frank, Ph.D. Professor Center for Chemosensory Sciences Oral Health & Diagnostic Sciences School of Dental Medicine University of Connecticut Graduate School MEDS 371: Systems Neuroscience 2011 Chemosensory Systems

2. OLFACTORY SYSTEM Purpose of Smell---Detect, Analyze Valuable or Dangerous Environmental Chemicals

3. Putrid camphoraceous: hexachloroethane floral: 2-amyl pyridine pepperminty: l-menthol ethereal: diethyl ether pungent: formic acid putrid: hydrogen sulfide musky: xylene musk Chemicals that Smell: Vapors, Names

4. Smell Prism Odor Qualities—One Set FRUITY geranial FOUL ethanethiol RESINOUS pinene FLOWERY phenethyl alcohol SPICY cinnamaldehyde BURNT acrolein

5. Peripheral Labeled Lines From Axel and Buck, 2005 Odor Receptors and Mitral Cells in Olfactory Bulb Red = ? Green = ? Blue = ?

6. From Buck, 2005 1000 GPCR odor receptors (OR)

7. Odor Transduction Adaptation, PKA Rapid Adaptation

8. Main Olfactory System -- Vomeronasal System Species Differences in Olfaction VNO = vomeronasal organ AOB = accessory olfactory bulb MeA = medial amygdala Dulac & Wagner, 2006 MOE = main olfactory epithelium MOB = main olfactory bulb AON = anterior olfactory nucleus PC = piriform cortex OT = olfactory tubercle LA = lateral amygdala EC = entorhinal cortex

9. Rodent Olfactory Bulb Glom = glomerulus, OSN = olfactory sensory neuron Inhibitory Neurons: PG = periglomerular cell, G = granule cell, Output Neurons: M = mitral cell lateral olfactory tract Schoppa and Urban, 2003 Rapid Adaptation Mixture Suppression OSNs

10. Olfactory Epithelium Cells, Turnover, Target in Olfactory Bulb

11. Sus = Sustentacular (supporting) cell, HBC = Horizontal Basal Cell GBC = Globose Basal Cell; mpp multipotent progenitor, ta = transit amplifying, inp = immediate neuronal precursor. OSN = Olfactory Sensory Neuron; i = immature, m = mature. Schwob, 2002. Olfactory Sensory Neuron Generation in Adults

12. Human Nasal Cavity, Sniffing Ortho- vs. Retronasal

13. MOE: Recordings, Apical and Basal

14. Morphological substrates for specific input-output functions. Functional Units in Olfactory Bulb ON = olfactory nerve PG = periglomerular cell M = mitral cell GR = granule cell AON = anterior olfactory nucleus Morphological substrates for inhibition.

15. Responses of Olfactory Bulb Neurons At top, phases of electro-olfactogram (EOG) are represented by Roman numerals (I, II, III, IV) (Kauer, 1974).  = stimulus delivery N = no response S 1, S 2 = suppression E 1, E 2, E 3 = excitation

16. Central Olfactory Pathways: Rodent AON: anterior olfactory nucleus, PC: piriform cortex, OT: olfactory tubercle, AM: anterior cortical amygdaloid nucleus, TER: lateral entorhinal cortex Rodents: Macrosmic >1000 OR

17. Odor stimuli to test with Monoclonal Nose in Mice. pine tar, turpentine rose-like lily pungent, orange nail polish, fruity ODOR CODING (+)/(–)

18. Mice with a “Monclonal Nose”… Fleischmann et al. 2008 ●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone) Go/No-go Fraction Correct Block of Trials Ethyl Acetate, –/+ Citronellol

19. Mice with a “Monclonal Nose”… Fleischmann et al. 2008 ●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone) Go/No-go Fraction Correct Block of Trials Ethyl Acetate, –/+ Pinene

20. Mice with a “Monclonal Nose”… Fleischmann et al. 2008 ●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone) Go/No-go Fraction Correct Block of Trials Acetophenone, Air

21. Block of Trials Go/No-go Fraction Correct See B Air Mice with a “Monclonal Nose”… Fleischmann et al. 2008 ●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone) Acetophenone = Air

22. Dulac, 2006 NATURAL SCENTS 100s of Chemical Components in Scent Representation in Few Glomeruli in Rodents Few Dominant Cues Inhibitory Interactions among Glomeruli

23. Central Olfactory Pathways: Human Humans:Microsmic ~300 OR

24. Odor Mixtures: Humans V = 5 mM vanillin, v = 1 mM vanillin R = 5 mM PEA, r = 1 mM PEA. 0 = water Gold background highlights correct responses of 10 subjects in each session The 31 adapt-test pairs were presented to each subject in each session Average % correct Identification for the 2 sessions is listed at right PEA = phenethyl alcohol odor Rose Single Compound Vanillin Mixture Component Single Compound PEA

25. ODOR CODING: Rapid Adaptation & Mixture Suppression From Frank et al, 2010 Single CompoundsMixture Components Controls

26. From Rolls, 2004 Convergence of Taste and Smell in Orbitofrontal Cortex From Rolls, 2004

27. Olfactory System Summary  Smell is a chemical sense that evaluates vaporous environmental chemicals.  We perceive many odor qualities, notes perhaps each associated with one of the hundreds of olfactory receptors (OR).  Olfactory sensory neurons (OSN) have dendrites with cilia containing a G-protien- coupled OR and axons that communicate to the olfactory bulb.  OSN can regenerate, giving them an unusual ability to recover from injury.  OSN located in separate regions use 4 subfamilies of OR, individual OSN express single OR variants, and all OSN expressing one of the hundreds of variants project to a few glomeruli in the olfactory bulb.  OSN may respond to many compounds, generating distinct spatial-temporal patterns of neural activity for each odor.  Olfactory bulb output neurons, mitral and tufted cells, relay olfactory signals to higher levels, and periglomerular and granule inhibitory neurons, which are generated throughout adult life, modify olfactory signals within the bulb.  Olfactory signals are relayed from the olfactory bulb to the olfactory paleo-cortex, then thalamus and cerebral cortex, where odor qualities are discriminated.  Projections to the hypothalamus and hippocampus are sites where experience and emotion interact with odor.

28. The End