Axon guidance Flashcards
how many neurons are in the human brain?
how many connections do each of these make? how many connections does that make in the brain?
10 to the power 11 neurons
each of these makes 1000 connections each
meaning there’s 10 to the power of 14 connections
how many extreme hypothesis theories are there for how the specific neuronal connectivity of the adult organism arises? name each one and say who proposed it.
there was 2 :
the resonance theory - Weiss
the chemoaffinity theory - Sperry
what is the resonance theory?
that stochatic (random) and diffuse neuronal outgrowth occurs to all targets followed by elimination of non- functional connections
what is the chemoaffinity theory?
that directed and specific outgrowth occurs through axons following “individual identification tags”carried by the cells and fibres of the embryo.
what happened during sperry’s experiment in 1963? what did this show? what has to be remembered?
the optic nerve was cut and the temporal retina removed.
this allowing just nasal axons to grow back
this proved that Sperry was right because the axons grew back directly to the right place, they ignored the territory that was normally innervated by other axons.
have to remember that this was during regeneration
If weiss was right how would you expect the axon pathways to be patterened?
Randomly
what is the pattern of axon outgrowth like?
it’s highly organised, reproducible and stereotyped.
what happens if in a chick embryo you cut and replace or reverse a segment of the neural tube before the motor axons grew out? what does this suggest?
despite displacement of cell bodies the motor axons T7 and LS1 still find their way to their normal muscle target.
this strongly suggests that axons can navigate to their targets.
what does the environment contain that allows axons to find their correct targets?
Guidance cues.
what is Cajal’s growth cone?
the growing tip of the axon which can sense cues in the environment.
this was proposed by cajal
why were early experiments on guidance cues done in insects?
why the grasshopper in particular?
because insects:
have a relatively simple NS
the embryos are easy to observe and manipulate.
the grasshoper was used as it’s larger this means that individual cells can be ablated using lasers.
what did early experiments to identify the locations of guidance cues find about axons pathways?
found that pathways by axons are stereotyped both from embryo to embryo and also from segment to segment
in the grasshoper what did detailed analysis of the experiment to locate guidance cues result in?
resulted in the identification of almost every neuron in the embryonic nerve cord, allowing a map of axon projections to be made.
what did reproducibility of axon behaviour in the grasshopper suggest?
when did pathways seem to change?
how was this tested?
suggested that growth cones responding to cues in the environment
the pathways seem to change when specific axons are encountered
this was tested by ablating cells that might carry potential cues.
during laser ablation, how can it be proved that the G-axon growth is looking for specific cues on the P - axon?
ablate the p - axon, the g-axon will stall.
know it’s not because of having a lack of axons to extend on to because there’s still the A axon with C axon extending onto it.
not due to a reduction of axons as if ablated the A axon instead of P then the G axon isn’t effected.
what is the labelled pathway hypothesis?
axons can selectively fasciculate with other axons, axonal surfaces carry labels or cues which different axon growth cones express different sets of receptors for the cues.
what do early axons (pioneer) do?
the form an axon scaffold on which later axons (followers) can extend.
what’s an example of axon scaffolds in vertebrates?
the subplate neurons in the mammalian cortex.
where do subplate neurons project prior to innervation of the cortex by the LGN (lateral geniculate nucleus) neurons?
what happnes if part of the subplate is ablated early on before the axons extend?
the subplate neurons project from the cortex to the thalamus.
if ablated before the axons extend the LGN innervation fails in the ablated region.
how to the pioneer axons find their way?
although it’s an apparently featureless environment, the pathways of pioneer axons are also stereotyped and growth cones appear to react at specific points in the pathway.
describe the pioneers pathways in the grasshopper embryo limb
the pioneer Ti1(tibial1) growth cone makes a specific turn at the limb boundry, and then again as it approaches the Cx1 cell.
what happens to the Ti1 pathway is Cx1 is ablated?
Ti1 growth cone stalls at the other side of the limb boundry
what are cells like Cx1 reffered to as?
stepping stones or guidepost cells
what does patterning information in the early embryo predict?
it predicts where axon tracts will form
what do forebrain axons follow?
what do hindbrain axons follow?
what do spinal cord axons follow?
forebrain axons follow boundaries of domains of patterning gene expression
the hindbrain axons follow the boundried of rhombomeres
the spinal cord axons are attracted to and follow boundaries of the floor plate.
where are axon guidance cues located?
in axons and many other cell types in the early embryo.
how have experiments suggested that guidance cues can be both positive and negative?
cell ablations lead to growth cone stalls - this is as if an attractive force has been lost.
Ti1 growth cone seems to avoid the limb boundry as if it were inhibitory
what are the 4 different ways in which guidance cues act?
contract attraction
contraction repulsion
chemoattraction
chemorepulsion
what are lamella made up of? are these stuck down?
they are made up of F-actin. the actin bundles are crosslinked into a net. No they are highly motile.
what are filopedia made up of? are these stuck down?
F- actin, the actin bundles are polarised to form larger bundles. No they are highly motile.
what are growth cones made up of?
growth cone made up of F-actin and microtubules.
what happens to F-actin in a resting growth cone?
what is sporadically dragged into the filopodia?
what happens when the cone comes into contact with an attractive cue?
F- actin treadmills in the resting growth cone.
in the resting growth cones, tubulin is dragged sporadically into the filopodia.
this happens much more dramatically when the growth cone comes into contact with an attractive cue.
what happens when the growth cone comes into contact with an attractive cue?
F-actintreadmilling slowsand F-actin accumulates.
the F-actin accumulation stabalises the filapodium and drags the microtubules into the back of the filopodium.
this means that growth cones don’t turn, they reorganise.
which part(s) of the growth cone is attached to the substrate?
the palm of the growth cone (the central domain) is attached.
the filipodium aren’t necessarily attached.
when a growth promoting cue is encountered, what two components lead to filopodial extension and reorientation of microtubules?
- Molecular clutch is engaged and rearward actin treadmilling slows.
resulting in forward movement of filopodium. - An Actomyosin-based actin-tubulin link pulls microtubules into the wake of extending filopodium.
Why is a stimulus of cue needed for forward movement?
this is needed to drive forward movement because attachment isn’t enough to rearrange the cytoskeleton.
how was it discovered that growth cones can be repelled as well as attracted?
mixtures of neurons in culture were found to fasciculate only with their own kind, this wasn’t due to attraction as when watched could see that the neurons were repulsed by each others axons Contact with each other’s axons led to growth cone collapse.
what does growth cone collapse do to F-actin?
it destabilised F-actin (the concentration of F-actin drops)
