Marion E. Frank, Ph.D. Professor Center for Chemosensory Sciences

1. University of Connecticut Graduate SchoolMEDS 371: Systems Neuroscience2011Chemosensory Systems Marion E. Frank, Ph.D. Professor Center for Chemosensory Sciences Oral Health & Diagnostic Sciences School of Dental Medicine

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

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

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

5. 1000 GPCR odor receptors (OR) From Buck, 2005

6. Adaptation, PKA Odor Transduction Rapid Adaptation

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

8. OSNs 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

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

10. Olfactory Sensory Neuron Generation in Adults 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.

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

12. MOE: Recordings, Apical and Basal

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

14.  = stimulus delivery N = no response S1, S2 = suppression E1, E2, E3 = excitation Responses of Olfactory Bulb Neurons At top, phases of electro-olfactogram (EOG) are represented by Roman numerals (I, II, III, IV) (Kauer, 1974).

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

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

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

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

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

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

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

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

23. 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

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

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

26. 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.

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