L10 - Axon Gudiance Flashcards
How many neurons does the human brain consist of?
Human brain consists of 1011 neurones
Each making >103 connections = 1014 connections
How does specific neuronal connectivity arise? - Weiss
Resonance theory – 1928
- Stochastic and diffuse neuronal outgrowth
- To all targets followed by elimination of non-functional connections
How does specific neuronal connectivity arise? - Sperry
Chemoaffinity hypothesis – 1939
- Directed and specific outgrowth
- Through axons following individual identification tags carried by cells/fibres of the embryo
Sperrys experiment
Cut optic nerve and remove temporal retina
- Allows just nasal axons to grow back
The regrowing axons grew though ignoring the territory normally innervated by the axons
- They grew back directly to the right place
Axon pathways
If Weiss were right - random patterns of axons in embryos
In reality the patterns of axon outgrowth are highly organised, reproducible and stereotyped
Experiment to test how axons are guided specifically to their targets in the chick
Cut and replace or reverse segment of neural tube before motor axons grow out
In mutant
- Despite displacement of cell bodies T7 and LS1 motor axons still reach normal muscle target
In control
- Normal innervation of specific limb muscles by motor axons from T7 and LS1
Shows axons can navigate to their targets
What are guidance cues?
Environment contains factors that axons use to find their targets
What we need to know about guidance cues?
Nature of guidance cues and where they are located
How axons detect and respond to them
What strategies are used so a limited number of cues can make a complex nervous system
What is Caias growth cone?
Growing tip of the axon sensed cues in the environment
Experiments to identify locations of guidance cues
Were done in insects
- Simple nervous system
- Embryos easy to observe and manipulate
- In larger insects individual cells ablated using laser
Grasshopper - map of axon projections
Detailed analysis resulted in identification of almost every neurone in the embryonic nerve cord - map of axon projections
Cues can be found on axons surface
Reproducibility of axon behavior suggested growth cones were responding to cues in environment
Pathways changed when specific axons were encountered
Tested idea that cues can be found on axons surface
Tested by ablating cells that might carry potential cues
G axon stalls in absence of P axon
- Not due to lack of axons on which to extend
- Not due to reduction in numbers of axons
- Because G axon growth cone looking for specific cues on P axon
Labelled pathway hypothesis
Axons
- Can selectively fasciculate with other axons
- Carry labels/cues
Different axon growth cones express different receptors for the cues
Axon scaffolds
Early axons (pioneers) form an axon scaffold on which later axons (followers) can extend
Axon scaffolds are important in vertebrates
Subplate neurons project from cortex to thalamus prior to innervation of cortex by lateral geniculate nucleus neurons
LGN innervation fails in this region
Ablating part of subplate early on before axons extend leads to?
LGN innervation fails in this region
First axon navigation
First axons navigate in an apparently featureless environment
Pioneers follow stereotyped paths
Pioneer axon growth cones appear to react at specific points in the pathway
Pioneers in Grasshopper limb
Pioneer Ti1 growth cone makes a specific turn
- At limb boundary
- As it approaches a specific cell (Cx1)
Ablation of Cx1 causes the Ti1 growth cone to stall at the other side of the limb boundary
Neither Cx1 or limb boundary cells are distinguished by morphological features
Other cells when ablated also cause stalling - guidepost cells
Implies there must be molecular differences in the environment
How to predict where axon tracts will form?
Use patterning information from the early embryo
Axon guidance cues are located on other axons and in many cell types in the early embryo
Forebrain axon tracts
Axons follow boundaries of domains of patterning gene expression
Spinal cord axon tracts
Axons are attracted to and follow boundaries of the floor plate
Hindbrain axon tracts
Axons follow boundaries of rhombomeres
Forces of axon guidance
Axon guidance cues may be both positive and negative
- Cell ablations lead to growth cones stalls - as if an attractive force has been lost
- Ti1 growth cone avoids the limb boundary - as if it were an inhibitory force
What are the 4 ways in which guidance cues act?
Contact attraction
Contact repulsion
Chemoattraction
Chemorepulsion
