Lecture 11 Axon guidance 1 Flashcards

1
Q

How many connections in brain and neurons

A

10^11 neurons with 10^3 connections so 10^14 connections

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2
Q

What are the two hypothesises for axon guidance?

A

WEISS: RESONANCE THEORY
SPERRY: CHEMOAFFINITY HYPOTHESIS

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3
Q

What was WEISS’ theory?

A

Stochastic (random) and diffuse neuronal outgrowth occurs to all targets followed by elimination of non-functional connections

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4
Q

What was SPERRY’s theory?

A

Directed and specific outgrowth occurs through axons following “individual identification tags” carried by the “cells and fibers” of the embryo

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5
Q

They both did tests on the visual system. What is the tectum?

A

tectum does preliminary visual processing, and controls eye movement

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6
Q

What is another name for tectum?

A

Superior colliculus

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7
Q

How are the axons between the eyes and tectum organised?

A
  • anterior retina (nasal) sends axons into posterior tectum
  • posterior retina (temporal) send axons into anterior tectum
  • same organisation on ventral/dorsal plane
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8
Q

Experiments were carried out on the tectum in

A

Newts then frogs

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9
Q

Why is the visual system organised like this?

A

so we see real images (correct orientation)

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10
Q

If SPERRY was correct, cutting the posterior retinal axons i.e. removing temporal retina and optic nerve, what would happen?

A

the anterior retinal neurons (nasal axons) would go to their normal location

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11
Q

If WEISS was correct, cutting the posterior retinal axons and optic nerve, what would happen?

A

there would be a diffusion of axons then elimination

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12
Q

Who was correct - Sperry or Weiss

A

Sperry

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13
Q

Does Sperry experiment show that axons are guided during development?

A

no, it was done on an ADULT frog, so it shows regeneration of axons show axon guidance

Cells were ablated and so some cells could remain allowing axons to follow the tracts

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14
Q

What other experiments did Sperry carry out

A

Extreme temporal and nasal ablation - axons went inbetween showing gradation of info varies dependent on the retinal axon ablated

Hence label directs growth –> FINE MAP

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15
Q

What would you expect to see if Weiss was right in embryo experiments and what was actually seen?

A

Expect random patterns of axons

Yet highly sterotyped organised reproducible

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16
Q

How do we know motor neurons are specifically guided to their targets in chick embryos?

A

In EARLY stage CHICK before MN have grown out

  • cut and replace, or reverse, segment of the neural tube before motor axons grow
  • when replaced in same orientation, motor neuron axons can still navigate to their normal targets
  • when replaced in reverse orientation, the axons still find their way to targets = suggests axons actively navigate
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17
Q

What are guidance cues?

A

Factors in environment that axons use to find their correct target

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18
Q

To learn more about axon growth, experiments were done in insects. Why?

A
  • simple NS
  • ease of observation/manipulation as large and dev outside body
  • in large insects like grasshoppers, individual cells could be ablated
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19
Q

What was found from axon growth experiments on insects

A
  1. Axon pathways are stereotyped from embryo to embryo and segment to segment
  2. they tacked and mapped axons which allowed them to located cues
20
Q

What did AB staining show in grasshoppers

A

Ventral nerve cord
Longitudinal axon fascicles
Commissures (Axon crossing)

21
Q

What was done to see where cues were located? What was found?

A

ablated nearby neurons to see if it affect axon pathway

  • it was found that most continued as normal
  • it was found that the G axon stalled in absence of the P axon as G axon looking for cues on P axon
22
Q

Reproducibility of axon behaviour in ablation suggests

A

Label in eco

23
Q

When do pathways change

A

When a specific axon is encountered

24
Q

Ablation studies showed that NOT

A

due to lack of axon on which to extend

due to decrease in number of axons

25
Q

What hypothesis do ablation studies support

A

Labelled pathway hypothesis

26
Q

This process was called labelled pathway hypothesis. What does this suggest?

A
  • Axons can selectively fasciculate with other axons
  • Axon surfaces carry labels or cues
  • Different axon growth cones express different sets of receptors for such cues
  • Early axons (pioneers) form an axon scaffold on which later axons (followers) can extend
  • Establishes axon surfaces as one potential source of guidance cue
27
Q

How come the first axons know where to go if it is thought the axons use each other to guide themselves?

A

the environment that is thought to be featureless has molecular differences that guide axons
- there are TFs that are already set up by the embryo (previous lectures) which the axons use to guide themselves

e.g. SHh and BMP in spinal cord on DV

28
Q

Describe axon scaffolds in vertebrates

A

Subplate neurons visual cortex
Project from cortex to thalamus prior to innervation of cortex by LGN. if ablate part of subplate early on, before axons extend LGN innervation fails here

29
Q

Give example in grasshopper of how pioneer cells follow sterotyped paths

A

limb - Pioneer tibial 1 (Ti1) growth cone turns at limb boundary as approaches CX1

Ablation of CX1 means GC stalls at other side of boundary

30
Q

Other cells in the grasshopper pathway like CX1 are called

A

Stepping stone or guidepost cells

31
Q

How are pioneer axons guided in the forebrain, hindbrain and spinal cord?

A
  • FOREBRAIN: Axons follow boundaries of domains of patterning gene expression
  • HINDBRAIN: Axons follow boundaries of rhombomeres
  • SPINAL CORD: Axons are attracted to, and follow boundaries of the floor plate
32
Q

Guidance of pioneer axons shows

A

Axons AND many embryo cell types contain guidance cells

33
Q

Guidance cues can be and examples

A

+/-

e. g. ablation - GC stall - attractive force lost
e. g. Ti1 GC avoid limb boundary - inhibitory

34
Q

What are the 4 forces of axon guidance?

A

Contact repulson/attraction

Chemoattractant/repulsion

35
Q

How do neurons know where to put their growth cones?

A
  • polarisation - one end is different to other in shape and function: due to different neurites
  • > axons - carry info away
  • > dendrites - receive incoming info
36
Q

How do axon microtubules differ to those of dendrites?

A

Axon MT highly organised as + GC and polarised

Dendrite MT less ordered and mixed orientation

37
Q

Why is there a difference in organisation of MT and axon/dendrite

A

Localisation of different types of MT associated proteins (MAPS)

38
Q

MT associated proteins for axons

A

TAU

39
Q

MT associated proteins for dendrites

A

MAP2

40
Q

What determines polarity

A

Neurite selection in hippocampus

41
Q

Define neurite

A

Any projection from cell body if immature neurite = axon or dendrite

42
Q

What marks where axons forming

A

GFP as +end directed kinesins Kif 1 mark

43
Q

How is a neurite selected to become a GC

A

Random after different neurites tried out

44
Q

Neurite to axon selection

A

microtubule (MT) stabilisation:

  • competition between neurites to stabilise MTs as removal casues another neurite to be selected
  • some kind of feedback loop to prevent other neurites being selected
45
Q

Difference between nascent and stabilised MT

A
Nascent = tyrosinated MT - dynamic MT
Stabilised = acetylated MT - only in newly polarised axons
46
Q

Taxol

A

Artifically stabilised MT causing neurite selection