Exam 4 - Neural Development Flashcards
Where do neurons come from?
They are produced from the neural tube or neural crest cells
Why are twice as many neurons produced than needed (100,000,000,000)?
Because many will die during development and it is better to have too many neurons than not enough
What regulates the cell migration that needs to occur in order for neurons to get where they need to be?
By hox genes and GABA
Where do synapses form?
Between neurons and target cells
Synapses are maintained/strengthened/lost under what principle?
Use it or lose it
Does synapse regulation only occur during embryonic development?
No, it continues throughout a persons lifetime
Where does axon and dendrite growth occur?
At the tip of a neuron in an area called the growth cone
What are microspikes (filopodia)?
They are extensions of a growth cone which act as “transient” feelers allowing for neurons to find their target cells. By feeling for adhesive molecules (CAM or extracellular molecules)
What happens when a microspike encounters a non-adhesive or even repellent molecule?
The microspike is rapidly withdrawn back into the growth cone
What happens when a microspike encounters an adhesive molecule?
A new growth cone will be set up there and the process will be repeated
In vivo, neurites must break through ECM surrounding the neuron, how do they accomplish this?
By secreting proteases, also axons are packed with microtubules allowing them to punch through the ECM
How do growth cones know what path to follow?
they follow the path of greatest adhesion
What forms the path of greatest adhesion which growth cones will follow?
A continuous pathway of extracellular matrix molecules (these molecules are likely produced by glial cells)
Which neurons can follow a ECM molecule pathway?
Only those containing the right substrate adhesion molecules (SAM)
What does it mean to say that these ECM pathways may be transient?
That it is likely that they only exist for a short period of time.
Why might the same ECM pathway need to be used for multiple neuron to target cells?
Because you don’t have enough genetic power to create a separate pathway for each
What are guidepost cells?
Rather than having a continuous adhesive ECM molecule pathway there are simply spots of adhesive ECM secreted by guidepost cells (glial cells)
How do guidepost cells work in directing a neuron to its target cell?
The growth cone extends microspikes in all directions and once it finds a guidepost a new growth cone is set up here. This process continues until the axon finds its target cell
What is the name given to the first neuron to use a guidepost cell pathway?
pioneer cell
How does contact guidance work?
Other axons in the same region as a pioneer cells may follow the pathway of the pioneer cell due to the high affinity that they have for it
How is contact guidance mediated?
Via CAMs or cadhedrins
Why is contact guidance inhibited once myelin sheets surround an axon?
Because myelin contains a protein called Nogo which is a repellent protein that inhibits regeneration.
How does the axon know where to veer off of the pathway and toward the target cell?
It is attracted to the target cell due to the fact that the target cell is secreting things like BMP
What happens to a neuron that does not successfully locate a target cell?
apoptosis
What mechanism kicks in as the growth cone nears its target cell?
chemotaxis
What is chemotaxis?
Movement toward highest concentration of some soluble signalling molecule secreted by target cells
What is the specific name of the chemotactic factors used in this mechanism?
They are neurotrophic factors
What two things are needed for any neural regeneration attempts?
- neurotrophic factors
2. a proper adhesive pathway to follow
Aside from their chemotactic function, what important role do NTFs have?
They promote neuron survival (trophic = feeding)
How are interneurons differentiated?
Due to the NTF, netrin that is produced by the floor plate. Netrin is both a chemotactic as well as a growth factor
What is reelin?
a NTF that has been studied in mice and found to be linked to Alzheimer’s in them
Aside from signalling and maintaining neurons, what other important function do NTFs have?
They signal oligodendrocytes to myelinate axons
The establishment of a synapse between an axon and a target cell is what kind of interaction?
It is a reciprocal interaction
Once the NTF has brought the axon right up to the target cell, what happens to the axon?
It is thought that the binding of the neurotrophic factor causes voltage-gated calcium channels to form, this promotes neurotransmitter release
What change in the target cell does NT release from the axon cause?
It cause NT receptors which are originally scattered around the entire cell to cluster on one part of the surface, which is where the synapse is forming
What does the growth cone become once it comes into contact with the target cell?
It becomes a nerve terminal
What is the junctional complex?
It is an ECM pad made up of agrin and dok-7 that allows fro the neuron and target cell to maintain a connection without direct contact
Where do newly synthesized nuerotransmitter receptors end up in a target cell?
They are placed directly on the surface of the cell that is a part of the synapse
How do neurons attach to the junctional complex?
Via a protein called neurexn
How do target cells attach to the junctional complex?
Via a protein called neuroligin
In studies done in mice, lack of the protien neuroligin has been connected to what neurological patholgoy?
Autism
How are memories likely regulated?
Through synapse formation and maintenance or loss of a synapse
Synapses that are used frequently are strengthened, what four ways is this accomplished?
- increase of agrin in junctional complex
- increase in NT concentration
- splitting the nerve terminal into multiple boutons
- formation of an extracellular net around the synapse allowing it to be held together firmly.
What three important things can be seen that indicate genetic diversity when comparing neurons in the brain?
- deletions
- duplications
- mutations
Where is most of the genetic variation among neurons found?
In the heterochromatin which is regulatory as opposed to coding regions