Module 1.2 Lecture 2 Synaptogenesis II

What are the three general features of the NMJ that have provided clues about the Molecular mechanisms of Synapse Formation?

Describe the first three stages of synaptic development

Muscle is not yet differntiated is all one tissue

The basal lamina is like an extracellular layer

In the nonsynaptic regions ECM proteins are used in support so your muscle has something to hold onto

The basal lamina between the synaptic cleft has synaptogenic machinery

Describe the last 2 stages of synaptic development

There are multiple motor neurons competing

One wins out and the other motor neurons don’t die, they just innervate a different muscle

For the next 3-5 years these neuromuscular junction advance

Describe the mature NMJ

Mitochondria are packed into the cells

Are there early indicators of synaptogenic indicators? How are AChRs synthesized?

It seems totally random where a motor neuron wants to form a synapse

What role does the basal lamina

Describe the denervation of the NMJ. What happens?

Describe what happens with persistent denervation and muscle elimination

Describe what happens following denervation of skeletal muscle fiber. Where is the expression of AChRs on the muscle surface concentrated? What about when re-innervation is prevented?

What properties do factors in the basal lamina have and what do they define?

Describe laminin Beta2 and where it is localized.

If you get an antibody against laminin beta2 and stain a neuromuscular junction. You will only see laminin?(I think) localized at the synaptic cleft.

When laminin beta2 was knocked out in mice what happened?

It served as a stop cell for the glial cell to not invade the synaptic cleft and also something relating to postsynaptic and presynaptic cleft

What is the neuron secreting to promote synaptogenesis? I.E How does the neuron tells the muscle. Describe it.

Experiment with rays (MuSK is muscle specific tyrosine kinase)

How AChR cluster in culture under control conditions vs addition of agrin? What does agrin do?

What happens with AChR clustering in agrin mutant NMJ?

How do you use genetics to block activity at the NMJ?

What happens in the Agrin/ChAT mutants and Agrin mutants?

How is agrin best understood?

How do axons sculpt the postsynaptic membrane? Who else helps align presynaptic terminals and AChRs?

How is AChR clustering locally regulated?

Homogenous cytoplasm

Who regulates the transcription of AChR genes and how?

What does denervation do to AChR gene expression?

The muscle knows it has been denervated and becomes like it is before it was denervated

How would you induce muscle paralysis if loss of muscle activity mimics denervation?

Still confused what the dispersive factor is. Might need to rewatch this lecture no clue whats happening should have read the book but exam next week.