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BMS381 Developmental Neurobiology > L6 - Making Maps > Flashcards

L6 - Making Maps Flashcards

1
Q

Hierarchy of the visual system

A

Object
Lens
Retina
Tectum

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2
Q

Nasal axons go

A

Posterior

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3
Q

Temporal axons go

A

Anterior

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4
Q

Main conclusion from the stripe assay

A

Posterior tectime makes a non permissive factor that repels temporal retinal axons

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5
Q

How was it determined that it was the temporal axons avoiding a repellant factor in posterior stripes

A

Activity abolished by heating posterior but NOT anterior membranes

Posterior membranes cause temporal growth cones to collaspe in vitro

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6
Q

What is the repellant factor produced in the posterior tectum

A

Two ephrins

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7
Q

Describe how the ephrins are expressed in the posterior tectum

A

Expressed in a gradient from lo anteriorly to hi posteriorly

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8
Q

Aside from ephrins there is a second gradient seen in the retina … what is this … describe the set up of this gradient

A

Eph receptor for ephrins A2 and A5

Expressed in a counter gradient from high temporally to low nasally

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9
Q

What is the effect of knocking out both ephrin A2 and A5

A

Temporal neurones project they axons to the posterior tectum and the topogrpahic map is distorted

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10
Q

Ephrin A2/A5 double knockout mice

A

Fail to make topographic maps

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11
Q

Describe how this tectum map is made in rodents

A

Intitial growth of all fibres throughout the tectum
Axon branching and synaptogenesis - THIS IS SENSITIVE TO THE EPHRIN GDT
Competition for synaptic partners involving electrical activity

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12
Q

Electrical activity can____________________ to _______________

A

Modulate responses

Guidance cues

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13
Q

Who conclued that electrical activity can modulate responses to guidance cues

A

Ming et al 2001

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14
Q

Describe what Ming et al 2001 concluded

A

Demonstrated that electrical stimulation can enhance of reverse the response to guidance cues

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15
Q

In whaat case does electrical stimulation enhance the response to guidance cues

A

Netrin

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16
Q

In whaat case does electrical stimulation reverse the response to guidance cues

A

MAG

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17
Q

Electrical sitmualtion leads to an increase in _________ in a _________ dependent manner

A

Increase cAMP

Ca dependent

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18
Q

So more stimulation leads to

A

More stable Ca elevation

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19
Q

Refinemnt of connections is …..

A

Activity dependent

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20
Q

In lower vert. where the intial map in the tectum is topographic - coarse grained and axons make contacts over large and overlapping areas of the tectum … What is seen at later stages?

A

Some contacts are lost and the map becomes more precise

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21
Q

The refinement of the topogrpahic map depends on what (2) things

A

Activity AND

Competiton

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22
Q

Cells that wire together

A

Fire together

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23
Q

The ‘cells that wire together fire together’ describes what mechanism

A

Mechanism of synapose elimination which involves the localised release of neurotrohpic factors - THIS IS THOUGHT TO BE ENHANCED WHEN TWO CELLS FIRE AT THE SAME TIME

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24
Q

Give an example of where the ‘wire together fire together’ does not explain development in that region

A

In the embryonic tectim (Superior colliculus) mapping takes place before the animal encounters any light

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25
Q

The embryonic retina is

A

Spontaneously active

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26
Q

In mammals what two compoenents work together to form the topographic map

A

Ephrins and electrical activity

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27
Q

As axons reach the tectum what happens to the retina

A

Becomes spontaneously active

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28
Q

What could one hypothesise regarding the retina becomming spontaneously active

A

Could be that Hebbian principles are already operating (as in the occular domainance columns)

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29
Q

Experimental evidence to support the fact that Hebbian principles already operating

A

Na channel blocker - TTX - blocks AP gen - blocks map refinement

Geneticially block nAChR - no map refinement

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30
Q

When are early exuberant projections pruned back by in mice

A

Post natal day 8

31
Q

Describe what is seen in mie which lack the B2 subunit of nAChR

A

Uncorrelated RGC activity (retinal waves are disrupted_ and their topogrpahic maps do not refine

32
Q

TTX applied …

A

Axon refinenment DOES NOT occur

33
Q

Describe the links to electrical activity and neurotrophins

A

Enhanced retinal activity - upreg BDNF

BDNF promotes RGC axon branching ONLY WHERE Eph-Ephrin interactions are low

34
Q

Downregulation EphrinA5

A

Increase in branching

35
Q

____________ and ________ interact physically in a__________________

A

Ephrins and Trks

Neurotrophin dependent manner

36
Q

Where else are topogrpahic maps used?

A

In the visual systems - RGCs - LGN

Also uses ephrins

37
Q

Describe how you represent a non-spatial sense like smell?

A

Olfactor information detected in the olfactory epithelium

1000+ olf receptors but each neurone only expresses the one

38
Q

Receptor expression is dispersed in the nasal epithelium how does this compare to the olfactory bulb

A

Axons become organised in the olfactory bulb

39
Q

Describe how mappying occurs from epithelium to the bulb

A

Neurones expressing the same receptor are able to converge on the same glomerulus

40
Q

What is IRES

A

Internal ribosome entry site

41
Q

What can IRES be used for

A

To express more than one gene

42
Q

LacZ encodes what

A

Beta galactosidase enxyme

43
Q

Receptor expression governs __________

A

Guidance

44
Q

What experiment could you use to demonstrate that where axons go is determined by which receptor is expressed

A

RECEPTOR SWAP EXPERIMENTS

When the P2 coding region is swapped for M71 axons go to normal M71 glomerulus

45
Q

What is the strucutre of olfactory receptors

A

7 TMD GPCR like molecules

46
Q

Early guidance of olfacotry neruones is ….

Describe what this means

A

Activitiy independent

Even in the absence of the ligand each receptor has a characterisitc basal signalling activity

47
Q

Neurones expressing the same olfacotr receptor will have

A

Similar basal cAMP level (adenylate cyclase dependent)

48
Q

Similar basal cAMP level (adenylate cyclase dependent) in ORS determines

A

Via CREB

This level of transcription of a family of guiace cues and receptors

49
Q

What types of guidsance cues are turned on

A

Robo/Slit

Neurophillin

50
Q

The guidance cues transcribed are known as

A

Type 1 molecules

51
Q

Type 1 molecule transcription results in

A

Characteristic type 1 protein level - receptors and cues

Are associated with expression of a particular olfactory receptor

Determines the mapping in the olfactor bulb

52
Q

Disruption of guidance cue expression

A

Disrupts regional mapping in olfacotry bulb

53
Q

Describe how continuous maps are converted to discrete maps

A

Axons entering the olfacotry bulb are pre sorted due to type 1 cue/receptor interactions
Activity independent

Cue expression switches with time so that early entering axons then guid the later entering

Sorting into glomeruli - activity dep -

Activity drives higher cAMP levels which turns on expression of type 2 cues

These interactions sort axons expression same ORs into groups to form glomeruli

54
Q

How do we know gomeruli sorting is activity dependent

A

Activity blocking reagents block the sorting

55
Q

What are some examples of type 2 cues

A

Homophillic adhesion molecules (Kirrels and contactins)

OR mutual replellents (Ephs and ephrins)

56
Q

SUMARY TO THE BULB

EARLY

A

Activity independent, pre target sorting

Olfactory receptor specific expression of TYPE 1 molecules

57
Q

SUMMARY TO THE BULB

KATE

A

Activity dependent glomerulus sorting

Olfactory receptor specific expression of type 2 molecules

58
Q

What is different when compared to the visual system about the pisiform cortex neurones

A

No spatial organisation

59
Q

What is interesting about spatial organisation of piriform cortex cells and mitral cells

A

They exhibit no spatial organisation

60
Q

PC

A

Piriform cortex

61
Q

PC neurons respond to multiple ….

A

Structurally dissimilar odorants

62
Q

The pirifrom cortex was suggested to be the

A

Site of olfactory learning

63
Q

Who tested the idea that the piriform cortex was the site of the olfactory leaening

What tool did they use

A

Choi et al 2011

Using optogenetics

64
Q

Describe the experimental startergy of Choi et al (2011) …

A

Introduce ChR2 into a subset of neruones
Can allow the PC neruones to fire without input from the mitral cells
Stimulation of ChR2+ neurones with light paired with an aversive/appetitive stimulus in unconditioned animals
After conditioning test whether light along

65
Q

What type of learning did Chois et al (2011) stratergy depend on

A

Classical associatev learning

66
Q

3 ways that ChR2 could be introduced into Piriform cortex neurones - pros/cons of each

A

1) Use a synapsin promoter - hits 50% of the cells
2) Infect floxed ChR2 into mouse into which Cre is driven by an Emx1 promoter restricted to excitatory neurones - hits 50%
3) Insert floxed ChR2 (which is flipped) at the same time as virus expressing Cre driven by synapsin - inverted floxing - much lower expresion rate (10%)

67
Q

Inverted floxing

A

Flip the origenation so that Cre will invert and insert a gene - NOT DELETE IT

68
Q

ChR2 has been shown to be able to

A

Conditon adversive behaviour

69
Q

How does ChR2 condition adversive behaviour

A

Photostimulation of ChR2 expression neurones in PC - CONDITIONED STIMULUS was paired with a footshock - UNCONDITONED STIMULUS
- on only one side of the chamber to conditon the animals

Animals exhibit flight behavour to CS alsone by only when ChR2 was present in the PC neurones

Conditioning with odorants and PS together showed that either PS or odorants could elicit flight

70
Q

What is the experimental eviidence that ChR2 photostiulation is able to drive appetitive behaviours?

A

Mice trained to take water in response to odorant could be retrained to respond to the PS

Male mice could be trained to associate presence of a female with either an odour as the CS of with PS as the CS

71
Q

Evidene to suggest piriform cortex neruones are plastic in associative learning capacity

A

Same set of ChR2 expressing PC neurones can be re trained in either direction

Distinct set of ChR2 expressing PC neurones can be trainined and retrained ti elicit different behaviours

This shows the piriform cortex is a VERY PLASTIC SUBSTRATE

72
Q

Does the evidence presented here prove the PC is the site of odorant learning?

A

No — it just shows the PC can be used for associative learning

73
Q

Are all responses to odorants learned?

A

A small subset of odours elicit innate responses

E,g. TMT from fox = fear

Spatially invartiant projections from OB to cortical amygdala that may be involved

BMS381 Developmental Neurobiology (16 decks)

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