Making a map of 'things' Flashcards
What is a map of ‘things’?
What kind of map?
Visual system
Spatial map - continuous information
What is a map of ‘not things’?
What kind of map?
Olfactory system
Discrete map - detect particular smells
What structure of the brain is the world mapped in?
The superior colliculus/tectum
What is the difference between the superior colliculus and the tectum?
SC - in mammals
T - in lower vetebrates
Where do the neurons from the different parts of the retina go to?
Why?
Nasal –> posterior part of tectum
Temporal —> anterior part of tectum
Because the lens flips the picture of the outside world, need to flip it back again
Describe the stripe assay
What does it show?
Alternating strips of anterior and posterior tectum challenged with strips of retina from nasal to temporal
Shows:
Temporal axons avoid posterior stripes
Why do the temporal axons avoid the posterior tectum?
Posterior tectum makes an INHIBITORY factor that repels the temporal axons
What inhibitory factor is made by the posterior tectum that repels the inhibitory factor?
Describe them
Two different ephrins
MEMBRANE BOUND
NON-permissive factor
How are ephrins expressed in the tectum?
Gradient from posterior (HI) to anterior (LO)
What are the receptors for ephrins?
Ephs
What are ephs are how are they expressed in the retina and how?
Receptors for ephrin A2 and A5
In a counter gradient from temporal (HI) to nasal (LO)
How do you know the organisation of the axons in the tectum are due to the temporal axons avoiding a repellant factor made by the posterior tectum?
- Activity is abolished in the posterior with heat treatment but NOT in the anterior
- Posterior membrane cause growth cone collapse in vitro
What happens in mice with ephrin A2 and A5 KO?
Temporal neurons project their axons to the posterior of the tectum and the topographic map is disordered
When KO ephrin A2 and A5 in rodents, what is unusual?
See a spotty distribution and see that NASAL axons are effected as well as temporal
Nasal neurons normally ignore ephrins
Why, in the mouse, are nasal axons affected by the KO of ephrins, but in the chick/frog, they aren’t?
Different things occur in the mouse and other mammals compared to in the chick/frog
In the chick/frog:
- Axons initially go to where previously described (nasal - posterior, temporal - anterior)
In mice/other mammals:
- Initial growth of ALL FIBRES through the tectum
- Subsequent branching and synaptogenesis is what is sensitive to ephrins
- More branching of the TEMPORAL axons towards the ANTERIOR, NASAL to POSTERIOR
How does the branching in the mouse tectum occur?
How do temporal axons become localised to the anterior of the tectum?
- Random competition between the axons for their synaptic partners (involving electrical activity)
- Weaker synapses become eliminated
Temporal –> anterior
- Temporal have higher levels of eph receptors –> more sensitive to ephrins
- Synapses made aren’t as good, don’t fire as well, get pruned back
Why do temporal axons occur throughout the tectum in the mouse in a ephrin KO?
No competitive disadvantage, synapses are better, continue to compete throughout the tectum for synapses
How can electrical stimulation effect the response to guidance cues?
Can enhance or reverse the response to guidance cues
What guidance cue response is enhanced using electrical stimulation?
Netrin
What guidance cue response is reversed using electrical stimulation?
MAG
What happens when electrically stimulate neurons in a low netrin concentration (which doesn’t normally turn growth cones)?
ENHANCES the response to netrin –> growth cones now turn
Causes SENSITISATION
What happens when electrically stimulate neurons in the presence of MAG?
Reversal:
Turn when is initially REPULSION into ATTRACTION towards MAG
Using the ratio of dye, what can be seen when electrical activity is applied to a neuron 10 pulses compared to 2 pulses?
Both have a rise in calcium but the rise after 10 pulses is more significant and sustained
How does electrical stimulation affect cAMP?
How does this occur?
Increase cAMP
This increase is calcium dependant
How does electrical stimulation of a neuron change how it responds to cues in the environment?
Electrical stimulation changes the CHEMICAL STATE oft eh cell
What is refinement of axon connections dependant on?
ACTIVITY
Describe the refinement of axons in the tectum of lower vertebrates (where initial map is topographic)
- Initially overlap between the nasal and temporal projections
- OVER TIME, overlapping contacts are lost and map becomes more precise
Refinement depends on ACTIVITY and COMPETITION between the axons
What happens if block activity in the cortex?
Poor refinement of projections alternating between one eye or the other
Overlapping projections
Cells that fire together..
…wire together
What does the mechansim of synapse elimination involve?
Localised release of neurotrophic factors from 2 cells firing at the same time
What is the neurotrophic factor released from cells firing together that strengthens their connection?
BDNF
When does tectal mapping occur?
Why does this raise questions?
Happens before birth - before the animal encounters any light
Before encounter light - where does the electrical activity come from to? (electrical activity needed to create maps and refine axons)
How does tectal mapping occur with no light?
How is this seen?
Retina become spontaneously active as axons reach the tectum
Hebbian principles already occuring?
Seen monitoring calcium levels using a dye
What happens in the tectum if treat with TTX?
What is TTX?
TTX - sodium channel blocker
Blocks action potentials and therefore map refinement
What happens in mice lacking beta2 subunit of nAChR?
What does this show?
Uncorrelated RGC activity
Unrefined topographic maps
Shows neural activity is required for map refinement
What does enhanced retinal activity result in?
BDNF up regulation
What does BDNF promote?
RGC axon branching in the tectum ONLY where the eph-ephrin interactions are low
What does down regulation of Ephrin A5 cause?
Increased branching in the tectum
What are the receptors for BDNF?
Trks
How do Ephs and Trks interact?
What does the interaction between Ephs and Trks cause?
In a neutrophin-dependant manner
Reduced PI3K and Reduced branching
Where are topographic maps and ephrin gradients used in the visual system
Tectum (superior colliculus)
MAMMALIAN RGCs
LGN
Where does the LGN receive input from?
What does this allow?
How is this different to the tectum?
BOTH eyes
Allows INTEGRATION of vision
Tectum - info from ONE eye
How are the inputs to the LGN arranged?
In layers
Alternative layers - alternated between the eyes
How are the RGC axons mapped onto the LGN?
TOPOGRAPHICALLY using gradient of ephrins
Predetermined
Describe the interaction between Trks and Ephrin A5 and how this is altered by Ephs (receptors)?
Trks and Ephrins interaction is dependant on neurotrophin
In the ABSENCE of Eph:
- Trk and ephrin A5 interation INCREASES PI3K and therefore branching
In the PRESENCE of Eph:
- This abolishes the PI3K increase and branching
- In CONCENTRATION DEPENDANT manner
What is the PI3K pathway important in?
Branching/axon formation
