Marion E. Frank, Ph.D. Professor

Center for Chemosensory SciencesOral Health & Diagnostic Sciences

School of Dental Medicine

University of Connecticut Graduate SchoolUniversity of Connecticut Graduate SchoolMEDS 371: Systems NeuroscienceMEDS 371: Systems Neuroscience

20112011Chemosensory Systems Chemosensory Systems

OLFACTORY SYSTEM

Purpose of Smell---Detect, Analyze Valuable or Dangerous Environmental Chemicals

Putrid

camphoraceous: hexachloroethanefloral: 2-amyl pyridine

pepperminty: l-mentholethereal: diethyl ether

pungent: formic acidputrid: hydrogen sulfidemusky: xylene musk

Chemicals that Smell: Vapors, Names

Peripheral Labeled Lines

From Axel and Buck, 2005

Odor Receptorsand Mitral Cells in Olfactory BulbRed = ?Green = ?Blue = ?

From Buck, 2005

1000 GPCR odor receptors (OR)

Odor Transduction

Adaptation, PKA

Rapid Adaptation

Main Olfactory System -- Vomeronasal System

Species Differences in Olfaction

VNO = vomeronasal organAOB = accessory olfactory bulbMeA = medial amygdala

Dulac & Wagner, 2006

MOE = main olfactory epitheliumMOB = main olfactory bulbAON = anterior olfactory nucleusPC = piriform cortexOT = olfactory tubercleLA = lateral amygdalaEC = entorhinal cortex

Rodent Olfactory Bulb

Glom = glomerulus, OSN = olfactory sensory neuronInhibitory Neurons: PG = periglomerular cell, G = granule cell, Output Neurons: M = mitral cell lateral olfactory tract

Schoppa and Urban, 2003

Rapid AdaptationMixture Suppression

OSNs

Olfactory Epithelium Cells, Turnover, Target in Olfactory Bulb

Sus = Sustentacular (supporting) cell, HBC = Horizontal Basal CellGBC = 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

Human Nasal Cavity, Sniffing

Ortho- vs. Retronasal

MOE: Recordings, Apical and Basal

Morphological substrates for specific input-output functions.

Functional Units in Olfactory Bulb

ON = olfactory nervePG = periglomerular cell

M = mitral cellGR = granule cell

AON = anterior olfactory nucleus

Morphological substrates for inhibition.

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

S1, S2 = suppression

E1, E2, E3 = excitation

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

OH

O

O

O

Beta-Citronellol

Alpha-Pinene Acetophenone

Ethyl Acetate

Odor stimuli to test with Monoclonal Nose in Mice.

pine tar, turpentine

rose-likelily

pungent,orange

nail polish,fruity

ODOR CODING

(+)/(–)

(+)/(–)

Mice with a “Monclonal Nose”… Fleischmann et al. 2008

●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone)

Go/

No-

go F

ract

ion

Cor

rect

Block of Trials

Ethyl Acetate, –/+ Citronellol

Mice with a “Monclonal Nose”… Fleischmann et al. 2008

●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone)

Go/

No-

go F

ract

ion

Cor

rect

Block of Trials

Ethyl Acetate, –/+ Pinene

Mice with a “Monclonal Nose”… Fleischmann et al. 2008

●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone)

Go/

No-

go F

ract

ion

Cor

rect

Block of Trials

Acetophenone, Air

Block of Trials

Go/

No-

go F

ract

ion

Cor

rect

See B

Air Air

Air Air

Mice with a “Monclonal Nose”… Fleischmann et al. 2008

●= control ▲ = transgenic, 95% ORN express M71 (ligand Acetophenone)

Acetophenone = Air

Dulac, 2006

NATURAL SCENTS

100s of ChemicalComponents in Scent Representation in FewGlomeruli in Rodents

Few Dominant Cues

Inhibitory Interactions among Glomeruli

Central Olfactory Pathways: Human

Humans:Microsmic~300 OR

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

SingleCompound

Vanillin

Mixture Component

SingleCompound

PEA

ODOR CODING: Rapid Adaptation & Mixture Suppression

From Frank et al, 2010

Single Compounds Mixture Components

ControlsControls

From Rolls, 2004

Convergence of Taste and Smell in Orbitofrontal Cortex

From Rolls, 2004

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.

The End