Sensory Encoding of Smellin the Olfactory System of MAMMALS

(reviewing “Olfactory Perception: Receptors, Cells, and Circuits” by Su et al, 2009)

Ben CipolliniCOGS 160

May 13, 2010

TODAY Compare / contrast!

Gross Pathways Receptor Neurons Glomeruli Output Neurons Higher centers

Gross Pathways

ORNs in antennae

Projection neurons from antenna lobe to lateral horn and mushroom body

Glomeruli in antenna lobe mediate most receptor-specific processing

Kenyon cells in mushroom body have sparse representation of odors for associative learning

Lateral horn has place-specific processing of sensory-motor associations

Keene & Waddel (2007)

Compare to MammalsShared Feature Insect Mammal

ORNs Antenna + maxillary palps

Olfactory epithelium

Glomeruli Antenna lobe Olfactory bulb

Output cells Projection Neurons

Mitral cells & Tufted cells

Classification & learning

Mushroom body Piriform CortexDM Thalamus

Behavioral outputs Lateral Horn Orbitofrontal ctx?

Quiz!

Olfactory Organs

Mammals: 4 organs Main Olfactory

Epithelium Vomeronasal Organ Grueneberg ganglion Septal organ of

Masera

Insects: 2 organs Antennae Maxillary Palps

Mammalian OlfactoryOrgans and Receptors

Main Olfactory Epithelium

MOE ORs for odor ID; 250-1200

functional genes

Trace amine-associated receptors (TAARs) can detect volatile urine-based amines; 15 in mouse (social cues)

Output to main olfactory bulbX

XX

Vomeronasal Organ

V1Rs (urine) for conspecific recognition, male sexual behavior, maternal aggression, regulation of female estrous cycles, stress level indicator

V2Rs (sweat and urine) for pregnancy blocking, individual / gender identity, aggression (from males), stress (from females)

Formyl Peptide Receptors (immune system) for health status

Outputs to accessory olfactory bulb

Gruenberg Ganglion

Trace amine-associated receptors (TAARs)

ONE V2R receptor

Responsive to mechanical stimulation (sniffing / air puffs)

Outputs to main olfactory bulb

X

Septal Organ of Masera

ORs for general alerting

Responsive to mechanical stimulation (sniffing / air puffs)

Outputs to main olfactory bulb

X

Insect Olfactory Organs and Receptors

Antennae

Keene & Waddel (2007)

Basiconic for odor recognition, repulsion behavior

60-340 Ors

A few Grs (CO2)

Coleoconic (function unknown)

Ionotropic receptors → derived from glutamate receptors!

Trichoid for pheromones

Maxillary Palps

Keene & Waddel (2007)

Basiconic sensillia for taste enhancement

The Evolutionary Story

Insects Finding homologies in species of the same

order can be challenging Probably fast evolution Mechanism (duplication & variation vs.

modification) unknown

NOTE: loss of a single OR doesn't necessarily eliminate associated behavior Ensemble encoding Different ORs coding for an odor at different

concentrations (helps with variable gain)

Review: Tuning Curves of ORNs

Hallem et al (2006)

Odorants are identified by the pattern of receptors activated

Including inhibition of tonic firing

Individual receptors are activated by subsets of odorants

Receptors lie along a smooth continuum of tuning breadths

Broadly tuned receptors are most sensitive to structurally similar odorants

Higher concentrations of odorants elicit activity from greater numbers of receptors

Odor intensity as well as odor identity is represented by the number of activated receptors

ORN Activity vs Concentration

Kreher et al (2008)

ORN Activity vs Concentration

Kreher et al (2008)

Evolution II: Pseudogenization

Humans 20-30% of ORs 90% of VRN1s 100% (so far) of

VRN2s (only 20 genes exist)

Aquatic vertebrates Only have OR class I

Terrestrial vertebrates Have OR class I & II

Dolphins Have class I 100% of OR class II

pseudogenized

For no particular reason...

3 cool properties of ORNs that were discussed in this paper: Temporal tuning curves Antagonistic ORNs! Insect ORNs are actually really weird!

Tuning Curves of ORNs (New):Temporal Dynamics

Different ORNs can have different temporal dynamics (even for the same odor)

A single ORN can have different temporal dynamics to different odors

Bruyne et al (2001)

Odorant tuning curves

Combinatorics: Antagonistic Inhibition

The perceived magnitude of an odorant mixture was neither additive nor a simple average of its components

Fell between these limits, due to:

Masking (i.e. modification of perceived odor) or counteraction (i.e. reduction of odor intensity).

Mixing some odorants led to the emergence of novel perceptual qualities that were not present in each individual odorant

Suggests that odorant mixture interactions occurred at some levels in the olfactory system

Observed at presynaptic ORN axons in olfactory bulb

Oka et al (2004)

Insects ORNs are CRAAAZY!

Insect odor receptors have 7 transmembrane domains and have long been assumed to be GPCRs.

BUT we see major major differences!

No G protein mutant has been found to suffer a severe loss of olfactory function.

The topology of the insect Ors is inverted relative to GPCRs.

Each OR also appears to form a heteromultimer with Or83b

A canonical OR (with Or83b), can form a “ligand-gated cation channel”

Due to an odorant-induced, rapidly developing, transient inward current, independent of G protein signaling

A second, slower and larger component to the odorant-induced inward current

Slower both in onset and decay kinetics

Is sensitive to inhibition by a GDP analog Siegel et al (1999)

ORN Transduction: “canonical” Odorant binds to the odor

receptor

Odor receptor changes shape and binds/activates an “olfactory-type” G protein

G protein activates the lyase - adenylate cyclase (LAC)

LAC converts ATP into cAMP

cAMP opens cyclic nucleotide-gated ion channels

Calcium and sodium ions to enter into the cell, depolarizing the ORN

• Calcium-dependent chlorine channels contribute to depolarization as well

G protein turned off by GDP Firestein & Menini (1999)

Review: Projection Neurons

Live in antenna lobe (~200 per)

Receive input from ALL ORNs of a single class (~50; ~25 from each side)

Despite convergent input, show broader odorant tuning than ORNs

Project out to “higher centers”: mushroom body & lateral horn

Tufted & Mitral Cells

Live in olfactory bulb

Receive input from ALL ORNs of a single class from a single side

Like insect projection neurons, show broader odorant tuning than ORNs

Like insect projection neurons, project out to “higher centers”

NOTE: only mitral cells project to posterior piriform cortex

Review: Glomeruli

In Antenna Lobe, one per odorant “class” (50)

Consist of: Axons of ORNs

Dendrites of projection neurons

Neurites (axons and dendrites) of local neurons

ORN inputs all from same “class”, come bilaterally

Kandel, Jessel, Schwartz (2000)

Mammalian Glomeruli

Glomeruli:

50:1 convergence

Pns input from 1

Interglomerular inhibition (local neurons)

Intraglomerular inhibition (local neurons)

5000:1 convergence

M/T input from 1

Interglomerular inhibition (granule cells)

Intraglomerular inhibition (juxtaglomerular cells)

INSECT MAMMALIAN

Review: Transformations

Two glomerular transformations:

Increasing signal-to-noise

Producing variable gain

PN / Kenyon Cell Transformations:

Decorrelation of ORN signals

Variable Gain Revisited Broader tuning widths and nonlinear amplification among projection neurons

are mainly due to strong ORN-projection neuron synapses

How?

Low Activity Amplification: Weak presynaptic ORN activity is sufficient to trigger robust neurotransmitter release and cause substantial PN responses.

High Activity Fall-off: Strong ORN activity leads to depletion of synaptic neurotransmitter.

How about mammals?

The strong synapses : due to presence of numerous synaptic vesicle release sites and a high release probability

High probabilities of vesicle release have also been found in the mammalian olfactory bulb

Sparse Coding in Kenyon Cells

Perez-Orive et al (2002)

IN THE LOCUST PNs (columns)

respond to most odorants; KCs (columns) respond to very few

“Population sparseness” - % of cells that do NOT respond to an odor (rows)

How Do Locust KCs Become Sparse?

High convergence (400:1, 50% of PNs!)

Weak unitary synaptic connections

Synaptic integration in (oscillatory) time windows

Voltage-gated channels amplify coincident spikes

High spiking threshold (50-100 coincident Pns)

Loss of oscillations in bees → no “fine” discriminations

Fig. 7 from Masse et al (2009)

Higher-level pathways

Posterior Piriform cortex does classification (like Mushroom body!)

Cells within PPC project to MOST areas that are connected to

This includes feedback projections to olfactory bulb

Johnson et al (2000)

Higher-level pathways

Olfactory Learning

Li et al (2008)