Olfaction Flashcards

1
Q

what is the biological function of olfaction?

A

survival: find and select food, avoid predator
communication: recognize members of family, mother/infant bond, identify territory, mating

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2
Q

structure of olfactory epithelium

A

mainly made up of olfactory receptor neurons (ORNs)
- Mucus (produced by bowman’s gland) and oderant binding proteins line the olfactory epithelium. Supporting cells keep ORNs in place.

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3
Q

why do we sniff?

A

only 5% of nose has epitheliam so sniffing maximizes coverage of air interact to portion of the nose
- ORNs are more densely distributed at the top of the nasal cavity, sniffing directs airflow to interact with more ORNs

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4
Q

olfactory detection system

A

basal epithelium (5-10cm) on the roof of the nasal cavity –> around 20 axons bundle to form olfactory fila –> fila pass through cribiform plate

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5
Q

bowman’s gland function

A

secretes mucus

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6
Q

ORN structure

A

cilia poking out

embedded in the mucus membrane

where the exchange takes place

when odorants come in when we breathe in, mucus and olfactory binding proteins work together to enhance the capture of the chemicals and allow them to hang out near the cilia of the ORNs

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7
Q

what does odor perception depend on?

A

the concentration of odorant

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8
Q

can humans track scents?

A

humans can track scents at low concentrations over long distances (slowly)

performance increases and mean speed increases with repetition; you can tune your system to enhance this one cue

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9
Q

whats the sensitivity of humans to odors?

A

5 parts per billion for ozone because of mucus + olfactory binding proteins

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10
Q

enantiomers and odors

A

produce different percpetions

D carvone- spearment/ L-carvone- caraway

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11
Q

olfactory receptor potentials

A

generated in the cilia of receptor neurons not SOMA

odorants evoke a large inward (depolar) current when applied to the cilia

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12
Q

What initiates the olfactory signal?

A

Odorant binding to odor receptor proteins on olfactory receptor neurons (ORNs).

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13
Q

What happens after odorant binding to the receptor?

A

The heterotrimeric G-protein Golf is activated, and its alpha (α) subunit dissociates to activate adenylyl cyclase III (ACIII).

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14
Q

What is the role of adenylyl cyclase III (ACIII)?

A

ACIII converts ATP into cyclic AMP (cAMP), leading to an increase in cAMP levels.

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15
Q

What occurs when cAMP levels increase?

A

Cyclic nucleotide-gated ion channels open, allowing the entry of sodium (Na+) and calcium (Ca2+), primarily calcium.

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16
Q

What is the result of ion channel opening?

A

The influx of ions depolarizes the olfactory neuron, and action potentials are generated in the axon hillock region.

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17
Q

What mechanisms are involved in returning the neuron to its resting state and adapting to further odorant detection?

A

concurrent increase in Ca2+ and activation of calcium/calmodulin-dependent kinase II

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18
Q

what happens if you inactivate any of the molecules in the odorant transduction cascade?

A

abolish the responses

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19
Q

critical components of all ORNs

A

AC III
cyclic nucleotide-gated channels
active G-protein (Golf)

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20
Q

role of GPCR in odorant transduction

A

GPCR binds odourant –> activate G protein –> G protein alpha separates from gamma/beta –> activated adenylate cyclase III (AC III) –> AC III hydrolyzes ATP and increases cAMP levels in the ORN –> cAMP opens the channel –> influx of positive ions –> since ORN is resting at -60, there is a depolarization; potassium leaves, sdium and calcium comes in

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21
Q

what is ORN signal carried by

A

the CNG channels
- amplified by calcium gated chloride channels and the sodium calcium exchanger (calcium in, 3 or 4 sodium out. net influx of sodium) (exchanging for positive ions gives a much slower depol)

22
Q

calcium-gated chloride channel

A

NA/K ATPase makes sodium leave and potassium come in

this gradient is used to drive NKCC1, which brings in sodium and gets rid of chloride

here, chloride channels are amplifiers (unlike in the brain stem) because of a different concentration gradient in the ORN (it makes chloride leave the ORN)

finally, you have the GABA, glycine or calcium-activated chloride channels (if you have high chloride inside then chloride will tend to leave the cell; neg ions leaving is a depol)

the other excitatory channels have calcium coming in, which is equivalent - both create depol

23
Q

what is the purpose of NKCC1?

A

is required to maintain high intracellular Cl-

used NFA (niflumic acid) to block calcium-activated chloride conductances

in the presence of NFA, the current evoked is much less

genetically knocking out NKCC1 has the same result

NKCC1 is needed to maintain high chloride gradient

24
Q

NKCC1

A

Transporter of Na, K and Cl into ORN, required to maintain high intracellular Cl-

25
Q

KCC2

A

When neurons mature they downregulate the NKCCl transporter and upregulate the KCC2 channel. This channel uses K+ outward movement (with the gradient) to move Cl- out (against its gradient)

26
Q

Calcium activated Cl currents (olfaction)

A

When calcium enters the cell via Na+/Ca2+ channel, it binds to a Ca2+ gated channel that allows for the efflux of Cl-, in turn causing depolarization

27
Q

Bestrophin 2 expression and role

A

Expressed in olfactory epithelium, co localized with Ca2+ activated Cl- channel. When knocked out of genome, it was discovered that it was not solely responsible for Ca activated Cl channel currents.

28
Q

Anoctamin 2 expression and role

A

Protein with 8 transmembrane domains, imaged on cilia. When knocked out of genome, smell was gone

29
Q

What task is used in KO mice to see if they can smell?

A

Go/no-go operant conditioning task.
Odor=lick (go)
no odor = no lick (no-go)
If they lick without the presence of an odor, they are punished.

30
Q

Are calcium activated Cl currents required for olfaction?

A

One paper says they are dispensable, another argues that ANO2 knockout mice require longer times to identify new odorants.

31
Q

Four hypothesis from Buck and Axel

A
  1. Odorant receptors are in the g-protein coupled family
  2. Receptor family could be large and diverse (multigene) or restricted
  3. Receptors are only expressed in the main olfactory epithelium
  4. They designed primers for conserved regions of the 700 base pair region of the putative receptor, using PCR they found that all fragments added up to >2500 base pairs
32
Q

what defines each ORN?

A

single type of receptor it expresses

33
Q

Olfactory receptor neurons characteristics

A

Unmyelinated, slow conducting, can distinguish more that 5000 odors

34
Q

Where are receptor potentials generate in ORNs?

A

In the cilia, odor stimulation to cell body does not produce much of a response. Helps measure stimuli in a systematic way.

35
Q

Distribution of ORNs in nose

A

Specific distributions across nasal concha (turbinates) to allow for maximum encoding of stimuli

36
Q

Combinatorial coding of olfaction and why its needed

A

We don’t have one receptor per odor, so activation of different combinations of ORNs give rise to the thousands of different scents we can recognize.

37
Q

A single odorant can _______

A

activate multiple types of ORNs

38
Q

Defining characteristic of ORN axons

A

Unmyelinated, go up through the cribriform plate

39
Q

Glomeruli

A

Sites in the brain’s olfactory bulb where signals from the smell receptors converge.

40
Q

Glomeruli projections

A

Project to a single primary dendrite of mitral cells and tufted cells that send their axons to the olfactory cortex

41
Q

What did imaging of rodent olfactory bulbs show?

A

Increased blood flow in glomeruli associated with the odor presented

42
Q

Where does the single primary dendrite of mitral and tufted cells synapse?

A

Synapses into a single glomerulus to receive inputs from ORNs, also makes reciprocal synapses with dendrites of periglomerular cells.

43
Q

What do secondary dendrites of mitral and tufted cells do?

A

Elongation in the external plexiform layer with reciprocal synapses with granule cell dendrites

44
Q

What do granule cells do in olfaction?

A

axonless inhibitory interneurons that constitute the majority of neurons in the vertebrate olfactory bulb. They provide the main source of interaction between the principal excitatory neurons of the bulb, the mitral and tufted cells

45
Q

What is different about the olfactory pathway into the brain?

A

Information not processed by thalamus first

46
Q

Sniff cycle

A

Proved wrong that olfaction existed on a slow time scale, sniff cycle gives rise to an internal timing mechanism for odor representation. When mouse mitral cell activity was temporally warped to account for inhalation/exhalation, showed higher firing rates in line with sniff cycle.

47
Q

Channelrhodopsin in ORNs

A

Helps us understand when an animal is detecting an odor. Light sensitive CH2 was used to activate specific ORN’s in a specific manor for a go/no-go task.

48
Q

Phase discrimination in CH2 ORNs

A

Used go/no-go task to see how well mice did when odors were presented close in time to one another. Higher latency in no-go signal gives better results.

49
Q

Vomeronasal organ

A

a portion of the mammalian olfactory system that is sensitive to pheromones

50
Q

Chemotopy

A

orderly mapping between odorant structure and spatial location of activated glomeruli

51
Q

Synthetic optogenetics odor paper

A

Used optogenetics and fake odors to train mice into recognizing information from a single glomeruli in patterns, then modified the pattern. Use go/no-go task with activation of mitral cells.