Axon Guidance I Flashcards
How many connections are in the brain?
10^14
What was Weiss’s hypothesis about the connectivity in adults?
RESONANCE THEORY
- Random connections and diffuse neuronal outgrowth occurs to all targets
- Followed by elimination of non-functional connections
- Activity of the neuron reinforces connection
When did Weiss state his hypothesis?
1928
What was Sperry’s hypothesis about the connectivity in adults?
CHEMOAFFINITY HYPOTHESIS
- Directed and specific axon outgrowth occurs through axons, following “individual identification tags” carried by “cells and fibres” of the embryo
- Chemicals are followed by growth cones
When did Sperry state his hypothesis?
1939
What is the superior colliculus termed in the Xenopus?
The tectum
When an object is seen, what happens as the image passes through the lens?
It is flipped, so that on the retina, the image is upside-down and back to front
How is the upside-down image on the retia flipped the correct way again?
The connections from the retina are organised so that:
- The axons from the nasal side of the retina (more ANTERIOR) go to the POSTERIOR of the tectum
- The axons from the temporal side of the retina (more POSTERIOR) for the ANTERIOR of the tectum
- There is a graduation of axons, corresponding topological mapping of the retina in the tectum, forming a fine map
What was the experiment done by Sperry to show that his hypothesis was correct?
- Cut optic nerve and removed temporal part of the retina (so that ONLY nasal axons can grow back)
- The regrowing nasal axons grew through but ignored the territory of the temporal axons
- He also ablated the edges of both the nasal and temporal neurons retina, only leaving the central retina
- Neurons grew back
- Shows that the mapping of the retinal ganglion in the tectum was graded
What would happen to the nasal neurons in Sperry’s experiment, if Weiss was correct?
The nasal neurons would grow everywhere and then be ‘pruned’ back
What did Sperry’s experiments show and not show evidence for?
- Neuron growth during axon regeneration
- Not what happens in the developing embyro
In regards to axon outgrowth, what happens in the embryo?
- Patterns of axon outgrowth which is highly organised. reproducible and stereotyped
- In the mouse, drosophila, zebrafish and human
What experiment was done to test if a specific neuron knew where to grow?
What was the control for this experiment?
- Reverse part of the spinal cord between T7-LS3 and see if the axons still know where to grown
- The motor axons still knew where to find their way to their muscle targets
- Showing that axons navigate to their targets and different neurons know where to send their axons
Control: Taking out this part of the spinal cord and putting it back in the same way
What are guidance cues?
Factors in the environment of a neuron which axons use to find their correct targets
What is a growth cone?
The growing tip of the axon which senses guidance cues in the environment
Who proposed the growth cone?
Cajal
Why were insects used to identify the location of guidance cues?
- Relatively simple nervous system
- Easy to observe and manipulate
- Can ablate the cells using lasers (in grasshoppers)
What did Corey Goodman discover?
In the grasshopper, identified almost every neuron in the embryonic nerve cord and draw a map of axon projections
How are development pathways in embryos the same?
Stereotyped from embryo to embryo and from segment to segment
Where can guidance cues be found?
On axons
What happens when a growth cone encounters an axon?
- Pathways change when axons encounter SPECIFIC axons
- Happens in a reproducible way
What is the ‘labelled pathway hypothesis’?
- Early axons (pioneers) form an axons scaffold on which later axons (followers) can extend
- Pioneer axon surfaces express some sort of guidence cue on their surface
- Axons join specific fasicles based on the type of cell adhesion they express
- Axons selectively fasciculate together (not random)
- Different axons carry different receptors for these cues
Where are subplate neurons found and what neurons do they provide scaffold for?
How is this proved?
- Project away from the cortes to the thalamus prior to the innervation of the cortex by the LGN neurons
- If ablate subplate neurons in area 17 before the LGN neurons extend - LGN neruons do not innevate this area
- Shows that the LGN neurons use the subplate neurons to EXTEND and use at GUIDANCE to get to the right place in the cortex
What do pioneer neurons supply for follower neurons and how?
A surface for them to extend on and provide guidance to get to the right places
They have guidance cues on their surface, which the receptors on the growth cone interact with to form facicles
- Contact attraction
