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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
The embryonic retina is
Spontaneously active
26
In mammals what two compoenents work together to form the topographic map
Ephrins and electrical activity
27
As axons reach the tectum what happens to the retina
Becomes spontaneously active
28
What could one hypothesise regarding the retina becomming spontaneously active
Could be that Hebbian principles are already operating (as in the occular domainance columns)
29
Experimental evidence to support the fact that Hebbian principles already operating
Na channel blocker - TTX - blocks AP gen - blocks map refinement Geneticially block nAChR - no map refinement
30
When are early exuberant projections pruned back by in mice
Post natal day 8
31
Describe what is seen in mie which lack the B2 subunit of nAChR
Uncorrelated RGC activity (retinal waves are disrupted_ and their topogrpahic maps do not refine
32
TTX applied ...
Axon refinenment DOES NOT occur
33
Describe the links to electrical activity and neurotrophins
Enhanced retinal activity - upreg BDNF | BDNF promotes RGC axon branching ONLY WHERE Eph-Ephrin interactions are low
34
Downregulation EphrinA5
Increase in branching
35
____________ and ________ interact physically in a__________________
Ephrins and Trks | Neurotrophin dependent manner
36
Where else are topogrpahic maps used?
In the visual systems - RGCs - LGN Also uses ephrins
37
Describe how you represent a non-spatial sense like smell?
Olfactor information detected in the olfactory epithelium | 1000+ olf receptors but each neurone only expresses the one
38
Receptor expression is dispersed in the nasal epithelium how does this compare to the olfactory bulb
Axons become organised in the olfactory bulb
39
Describe how mappying occurs from epithelium to the bulb
Neurones expressing the same receptor are able to converge on the same glomerulus
40
What is IRES
Internal ribosome entry site
41
What can IRES be used for
To express more than one gene
42
LacZ encodes what
Beta galactosidase enxyme
43
Receptor expression governs __________
Guidance
44
What experiment could you use to demonstrate that where axons go is determined by which receptor is expressed
RECEPTOR SWAP EXPERIMENTS | When the P2 coding region is swapped for M71 axons go to normal M71 glomerulus
45
What is the strucutre of olfactory receptors
7 TMD GPCR like molecules
46
Early guidance of olfacotry neruones is .... Describe what this means
Activitiy independent Even in the absence of the ligand each receptor has a characterisitc basal signalling activity
47
Neurones expressing the same olfacotr receptor will have
Similar basal cAMP level (adenylate cyclase dependent)
48
Similar basal cAMP level (adenylate cyclase dependent) in ORS determines
Via CREB | This level of transcription of a family of guiace cues and receptors
49
What types of guidsance cues are turned on
Robo/Slit | Neurophillin
50
The guidance cues transcribed are known as
Type 1 molecules
51
Type 1 molecule transcription results in
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
Disruption of guidance cue expression
Disrupts regional mapping in olfacotry bulb
53
Describe how continuous maps are converted to discrete maps
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
How do we know gomeruli sorting is activity dependent
Activity blocking reagents block the sorting
55
What are some examples of type 2 cues
Homophillic adhesion molecules (Kirrels and contactins) | OR mutual replellents (Ephs and ephrins)
56
SUMARY TO THE BULB EARLY
Activity independent, pre target sorting | Olfactory receptor specific expression of TYPE 1 molecules
57
SUMMARY TO THE BULB KATE
Activity dependent glomerulus sorting Olfactory receptor specific expression of type 2 molecules
58
What is different when compared to the visual system about the pisiform cortex neurones
No spatial organisation
59
What is interesting about spatial organisation of piriform cortex cells and mitral cells
They exhibit no spatial organisation
60
PC
Piriform cortex
61
PC neurons respond to multiple ....
Structurally dissimilar odorants
62
The pirifrom cortex was suggested to be the
Site of olfactory learning
63
Who tested the idea that the piriform cortex was the site of the olfactory leaening What tool did they use
Choi et al 2011 Using optogenetics
64
Describe the experimental startergy of Choi et al (2011) ...
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
What type of learning did Chois et al (2011) stratergy depend on
Classical associatev learning
66
3 ways that ChR2 could be introduced into Piriform cortex neurones - pros/cons of each
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
Inverted floxing
Flip the origenation so that Cre will invert and insert a gene - NOT DELETE IT
68
ChR2 has been shown to be able to
Conditon adversive behaviour
69
How does ChR2 condition adversive behaviour
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
What is the experimental eviidence that ChR2 photostiulation is able to drive appetitive behaviours?
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
Evidene to suggest piriform cortex neruones are plastic in associative learning capacity
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
Does the evidence presented here prove the PC is the site of odorant learning?
No --- it just shows the PC can be used for associative learning
73
Are all responses to odorants learned?
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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