Olfaction

Question 1

Why is the mammalian olfactory bulb molecularly and anatomically specialised?

Answer 1

To detect and discriminate a wide variety of odor molecules

Question 2

How do mammals cope with the diverse structural features of odorant molecules?

Answer 2

Express up to 1000 different odorant receptor (OR) genes on the cilial membrane surface of ORNs, each of which expresses only a single type of OR

Question 3

Why does the central olfactory system integrate signals from a large variety of odorant receptors?

Answer 3

Because a single object, such as the jasmine flower, emits a specific combination of dozens of different odour molecules

Question 4

What does the OB contain?

Answer 4

Thousands of signal-processing units, called glomeruli (1800 in the mouse), within which axons of ORNs form excitatory synaptic connections on the dendrites of mitral and tufted cells

Question 5

What do glomeruli together with their associated neurons (glomerular modules) essentially function as?

Answer 5

Axon convergence centers for inputs originating from one type of OR, propagating odorant-specific signals to mitral and tufted cells

Question 6

How is the odour molecule information subsequently processed?

Answer 6

By local neuronal circuits that mediate synaptic interactions within the glomerular module as well as between other such modules in the OB

Question 7

What layers can the OB be divided into?

Answer 7

Olfactory neuron layer, glomerular layer, external plexiform layer, mitral cell layer, internal plexiform layer and granule cell layer

Question 8

What was shown by intensive Golgi analyses in the 1970s? (ref)

Answer 8

Succeeded in visualising the morphology of neurons in each layers, and showed that the distinct layers were composed of morphologically distinct cells (Price and Powell, 1970)

Question 9

Where do the four zones of the OE extend from?

Answer 9

Dorsomedial to ventrolateral part, based on the type of OR that is expressed there

Question 10

What did the structural comparison of various odorant receptors reveal? (ref)

Answer 10

ORs with highly homologous amino acid sequences tend to colocalise in the same zone of the OE (Malnic et al. 1999)

Question 11

What did immunohistochemical approaches indicate?

Answer 11

This zonal arrangement is retained to some degree in the OB, ORNs in any given zone project to glomeruli situated in a spatially segregated corresponding zone in the OB

Question 12

Where is information received by sensory neurons in a given zone transmitted?

Answer 12

Glomeruli, and then mitral and tufted cells in corresponding zone of the OB

Question 13

What did examination of MC and TC tuning specificities show?

Answer 13

Glomeruli representing ORs with similar tuning specificty are assembled ina local region within a specific zone

Question 14

Where do ORNs expressing the same type of OR project their axons into? (ref x 2)

Answer 14

A few defined glomeruli with high convergence ratios (up to 5000:1) as demonstrated by in situ hybridization of OR mRNA in the OB, and targeted knock-outs and knock-ins of OR types (Vassar et al., 1994; Wang et al., 1998)

Question 15

What have physiological studies suggested about the glomerular convergence pattern? (ref)

Answer 15

One of the plausible models for explaining the tuning specificity of mitral and tufted cells (Mori et al., 1992)

Question 16

Why does the tuning specificity of MCs and TCs strongly reflect that of the glomerulus they occupy?

Answer 16

Because individual MCs and TCs project a single primary dendrite to a single glomerulus

Question 17

What is cruical for processing of molecular information in the OB?

Answer 17

The local assembly of glomerular modules with overlapping specificities to odor molecules

Question 18

What did Katoh et al., 1993 show?

Answer 18

Using a battery of odor molecules with systematic variations of molecular conformation, demonstrated that the MRR of individual MCs and TCs consists of a range of odor molecules that share characteristic structural features

Question 19

What are characteristic structural features?

Answer 19

Stereochemical structure of the hydrocarbon chain as well as the type and position of the attached functional group

Question 20

What did Johnson et al. 1999 find?

Answer 20

Responses to organic acid oddorants with varying hydrocarbon chain lengths were clustered in paired modules that respond to the acid functional group, but the focus of activity moved ventrally with additional carbons in the aliphatic structure

Question 21

What do these properties interact with?

Answer 21

Specific amino acid residues to differing degrees within binding pockets of ORs (Singer and Shepherd, 1994), providing a possible mechanism for the mapping of odour space onto the neural space

Question 22

What can a glomerular module be thus viewed as?

Answer 22

A molecular feature-detecting unit, with individual odorants activating a specific combination of these units

Question 23

What supports this (molecular feature-detecting unit)

Answer 23

Results of spatial mapping of glomerular activity after stimulation of the OE with a single odor compound as measured by 2-deoxyglucose uptake, cFos expression and fMRI

Question 24

How do glomerular modules within the OB interact with each other?

Answer 24

Through local neuronal microcircuits by local interneurons, granule cells and periglomerular cells

Question 25

What is each glomerulus in the OB composed of?

Answer 25

Two distinct anatomical compartments: one compartment (the ON zone) contains the terminal processes of ORNs, and the other (non-ON zone) lacks these processes and is instead occupied by the apical dendrites of bulbar neurons

Question 26

Where do PGCs extend their dendrites to?

Answer 26

Some extend their dendrites to both zones (type-I) but the majority extend only to the non-ON zone (type-II)

Question 27

What do PG neurons do?

Answer 27

Inhibit MCs; in particular, the type I PGCs deliver feedforward inhibition directly onto MC dendrites within the same glomerulus

Question 28

What is PGC inhibition mediated by?

Answer 28

Activation of PGC spines that release GABA onto the MC dendrites in parallel to their excitation by glutamatergic ORN input, providing a shunting inhibition that regulates the receptive fields of MCs

Question 29

When do MCs exhibit net activation?

Answer 29

When stimulated by odor ligands with the highest affinities for their associated ORs

Question 30

What do lesser degrees of ORN activation lead to?

Answer 30

Incur a net inhibitory response in which PGC-mediated inhibition of the MC overcomes its direct excitation

Question 31

What is seen in the odor-evoked activity patterns across MC ensembles?

Answer 31

Sparser and less overlapping (decorrelated) than the corresponding primary representations observed amongst ORNs

Question 32

What did Cleland and Sethupathy (2006) show?

Answer 32

Odor-evoked activity patterns are independent of the physical location of individual glomeruli within the OB, suggesting a non-topographical mechanism of contract enhancement

Question 33

When do mitral/tufted cells receiving monosynaptic input from ORNs generate spike bursts?

Answer 33

If the ORN-evoked EPSP reaches threshold for spike generation - thereby amplifying suprathreshold sensory input at the first stage of synaptic transfer in the olfactory system

Question 34

Where are reciprocal dendrodendritic synapses formed?

Answer 34

The signal horizontally backpropagates through the secondary dendrites into the EPL, forming reciprocal dendrodendritic synapses with GABAergic granule cells and other inhibitory interneurons, such as sSA cells

Question 35

What is lateral inhibition? (ref)

Answer 35

GCs receive excitatory glutamatergic input from basal dendrites of mitral/tufted cells and release GABA, effectively blocking activity of other mitral/tufted cells in the EPL (Xiong and Chen, 2002)

Question 36

What does the lateral excitatory network of tufted and sSA cells do? (ref)

Answer 36

Integrates heterogeneous activation levels across the bulbar input layer and delivers a uniform level of excitation to a subclass of PGCs. These, in turn, inhibit MCs, such that MC patterning relects relative, rather than absoulute, levels of glomerular activation in the OB (Cleland et al., 2007)

Question 37

What does global feedforward inhibition contribute to?

Answer 37

The normalization of the intensity of sensory input, which is essential for segregating quality from concentration effects and for constructing intensity-dependent representations of stimulus quality

Question 38

What is the benefit of global feedforward inhibition?

Answer 38

It likely improves the olfactory system’s ability to recognise the same odor at different intensities, while avoiding high rates of spiking to conserve metabolic energy

Question 39

What properties do MCs exhibit?

Answer 39

Intrinsic bistable and oscillogenic properties that influence their responses to specific odor stimuli

Question 40

When are these intrinisc subthreshold membrane potential oscillations and bursting properties apparent?

Answer 40

Even in the presence of blockers of GABAergic and glutamatergic transmission, and the oscillation is highly correlated to the membrane potential

Question 41

What did Desmaisons et al 1999 propose about these oscillations?

Answer 41

They are generated by a TTX-sensitive current - most likely candidate is the non-inactivating sodium current due to its similar activation threshold to intrinisc mitral cell oscillations (-70mV)

Question 42

How can the frequency be modulated?

Answer 42

It can be increased (or decreased) by making the current, as well as the slow potassium current, larger (or smaller)

Question 43

What is the benefit of having a frequency range?

Answer 43

Having a range of frequency in the driven subthreshold osccillations is important for the generation of gamma oscillations when the firing rate is low

Question 44

What have OB slice experiments revealed (ref)?

Answer 44

Synchronized subthreshold oscillations in MCs influence the timing of spontaneous and evoked APs (Desmaisons et al., 1999)

Question 45

If axons from two mitral/tufted cells belonging to different glomeruli converge onto the same target neuron in the olfactory cortex…

Answer 45

… the cortical neuron may act as a coincidence detector whose activity depends on the combined activation of the two glomerular modules

Question 46

What is the utility of synchronization of spike discharges?

Answer 46

Could enhance the probability of driving the cortical neuron because of the temporal summation of synaptic inputs from two mitral/tufted cells

Question 47

What is responsible for the generation of the oscillatory local field potential? (ref)

Answer 47

Dendrodendritic synaptic connections between mitral/tufted cells and interneurons (e.g. GCs) consisting of an excitatory synapse directly adjacent to an inhibitory MC-GC synapse (Shepherd et al., 1998)

Question 48

What do spontaneous IPSPs generated at dendrodendritic synapses do?

Answer 48

Effectively reset the phase of subthreshold oscillations and can lead to “rebound spikes” with constant latency, thereby synchronizing MC subpopulations during the processing of olfactory information