Neuromuscular Junction Flashcards
What is synaptogenesis
Formation of the synapse
The neuromuscular junction (NMJ) comprises portions of what 3 cells
- Motor neuron
- Muscle fiber
- Schwann cell
True or False:
The motor nerve terminal is specialized for NT release
True
What are used for energy involved with synthesis and release of NT
Mitochondria
Where is there a high concentration of AChRs on the postsynaptic cell
Clustered at the top of the folds
Where are voltage gated Na+ channels located on the postsynaptic cell
In the depression of folds
What do the Schwann cells do for the NMJ
Provide insulation and nourishment
Where do myoblasts originate from
The somite
Where do motor axons arise from
Somata
Where do Schwann cells arise from
Neural crest cells
True or False:
Neural crest cells are the precursor to Schwann cells
True
What do myoblasts turn into
Muscle fibers
Do myoblasts, motor axons, and Schwann cells travel short or long distances to create the NMJ
Long distance
True or False:
Early connections are none specific and go through a period of differentiation
True
True or False:
At birth the NMJ is fully functional and multiply innervated
True
Where do motor axons originate from
Neural tube
What do myoblasts turn into before muscle fibers
Myotubes
What does nerve to muscle contact lead to (2)
- Early synaptic transmission
2. Postsynpatic membrane differentiation
When do vesicles start to form in the presynaptic cell
As soon as the presynaptic cell touches the motor end plate
True or False:
AChRs subunits are expressed at low levels in myoblasts
True
Are the AChRs subunits slowly or quickly upregulated on the nerve to muscle contact
Quickly
What are the 3 way AChRs subunits are quickly upregulated
- AChR clustering
- Transcriptional activation of AChR subunit genes by sub-synaptic nuclei
- Transcriptional repression of AChR subunit genes by non-synpatic myonuclei
What are the 3 pathways that are implicated in the process of postsynaptic differentiation
- Agrin interacts with MuSK
- Neuregulin interacts with erbB kinases
- Activation of AChRs which stimulates voltage gated channels allowing for Ca++ to enter the cell
What does agrin interacting with MuSK do
Organize rapsyn mediated clustering
What does neuregulin interacting with erbB kinases do
Induce expression of AChR subunit genes in subsynaptic nuclei and eventually upregulate AChR
What does stimulation of voltage gated channels allowing more Ca++ to enter the cell do
Leads to repression of AChR expression in extrasynaptic nuclei
What happens if you do not have agrin
AChRs fail to cluster in the forming NMJ
True or False:
Agrin is a master organizer
True
What does MuSK act like
A second messenger the joins and phosphorylates interacting with rapsin
True or False:
Rapsin is an anchoring protein
True
How does the Ca/CAM system effect AChRs formation
Causes repression
What do the AChRs do in early embryogenesis and when does this occur
Cluster forming a plaque (17 days in embryo)
What happens to the plaque as the AChR density increase and when does this occur
The borders sharpen and length decreases (0 days postnatal)
What happens to the plaque postnataly and when does this occur
It perforates to form a pretzel like structure (5-30 days postnataly)
How do the junctional folds run in relation to each other
Parallel
How are the junctional folds spaced out in relation to one each other
Equally spaced
How do the junctional folds run in relation to the muscle fibers
Orthogonal or at right angles
True or False:
AChRs are densely positioned at the rest of the folds closely opposed by ACh active zones
True
What do the voltage gated Na+ channels do in the valleys of the junctional folds
Amplify synaptic current
How do the voltage gated Na+ channels amplify synaptic current
By lowering the threshold for an AP
What is the function of the basal lamina
It is an anchoring structure
Do junctional folds occur quickly or over weeks or months
Over weeks or months
When does transmission start to occur
When the growth cone contacts the myotube
What do the junctional folds help with
Stregnthening the connection and making the NMJ functional
What is one function of MuSK
Initiate the process of rapsyn anchoring AChRs to the membrane
What does rapsyn allow for
AChRs to be directly under an active zone
How are muscle fibers innervated at birth
Multiply innervated
How long does it take synaptic terminals to begin to segregate
Days
At what point are most muscle fibers innervated by one input
2 weeks
Is synaptic elimination a stereotyped response
Nope
What synapses are subject to elimination
Only those that fire an action potential
True or False:
Synapse elimination is competitive and depends on the activity of neighboring synapses
True
What are the 3 ways synaptic elimination occurs
- Synaptomedian model
- Synaptotrophin model
- Synaptotoxin model
What is the synaptomedian model
Retrograde signaling may differentially reward or punish competing axons
What is the synaptotrophin model
Decrease in trophic factors necessary to maintain synapse
What is the synaptotoxin model
Damaging toxins destabilize the nerve terminal thus leading to retraction of losing input
What is BDNF important for
Maintenance of synapse
What happens if there is less BDNF
The axon retracts
What may agrin function as in the synaptotoxin model
Protease inhibitor
What is agrin responsible for at the motor terminal
Forming and inhibiting axons
What contacts the muscle fiber first Schwann cell, motor axon, or myoblasts
Motor axon
