Target Innervation and Synapse Formation

Question 1

What are the steps of how an axon finds it target cell (target selection)?

Answer 1

1. Defasciculation (axons unbundle)
2. Enter, branch
3. Find topographic location
4. Find layer
5. Connect with target cells

Question 2

What molecules are involved with target selection

Answer 2

Step 1. NCAM
Step 2. BDNF, Semaphorin 3A
Step 3 & 4. Ephrins
Step 5. Cell adhesion molecules

Question 3

What are the 3 steps in synapse formation?

Answer 3

1. Target selection by the growth cone
2. Generation of the postsynaptic apparatus in the target cell
3. Differentiation of the growth cone into a presynaptic nerve terminal

Question 4

What does synapse formation depend on?

Answer 4

It depends on bidirectional reciprocal communcation between the presynaptic neuron and the postsynaptic target cell

Question 5

What model allowed us to learn so much about synapse formation? Why that model?

Answer 5

We learned through research on NMJ because of its simplicity, size, and accessibility

Question 6

How many stages are there in the development of NMJ?

Answer 6

5 stages of development

Question 7

What happens during 1st stage of development of NMJ?

Answer 7

Growth cone approaches muscle fiber

Question 8

What happens during 2nd stage of development of NMJ?

Answer 8

Growth cone adapts to surface of muscle fiber

Question 9

What happens during 3rd stage of development of NMJ?

Answer 9

A) muscle fiber area undergoes indentation.
B) vesicles cluster in active zones
C) basal lamina is formed
D) acetylcholine receptors on muscle fiber start to cluster

Question 10

What happens during 4th stage of development of NMJ?

Answer 10

A) 2nd innervation by a second axon
B) Schwann cell ensheathment
C) nuclei in synaptic area show increased AChR expression levels

Question 11

What happens during 5th stage of development of NMJ?

Answer 11

A) elimination of 2nd innervation
B) formation of junctional folds
B) complete ensheathment by basal lamina

Question 12

What are the 3 mechanisms of increasing AChR density at synapse?

Answer 12

1. AChR clustering
   2a. activation of AChR expression close to terminal
   2b. repression of AChR expression outside of the terminal area
2. AChR stabilization

Question 13

What are the mechanisms of decreasing AChR density at synapse?

Answer 13

electrical activity

Question 14

What triggers AChR clustering?

Answer 14

Neural agrin from basal lamina. It actives to tyrosine kinase MuSk which recruits rapsyn (R)

Question 15

What triggers AChR expression?

Answer 15

Neuregulin binds erb receptor tyrosine kinase

Question 16

What represses AChR expression in non-synaptic areas?

Answer 16

Neural activity; depolarization opens voltage-dependent Ca channels. Ca signaling regulates AChR expression

Question 17

In embryonic cells, muscle fibers are innervated by multiple axons. After birth, the fibers are only innervated by one, what happened?

Answer 17

In embryonic stage, several axons from different neurons converge on a myotube. But after birth, all but one synapse per fiber are eliminated. So one axon can attach to multiple muscle fibers, but muscle fiber only has one axon.

Question 18

What regulates removal of polyneural innervation?

Answer 18

electrical activity and growth factors

Question 19

What is the difference between CNS synapse formation and NMJ formation?

Answer 19

CNS synapse formation is less understood

Question 20

How is CNS synapse formation similar to NMJ

Answer 20

1) different steps
2) bidirectional exchange of signals
3) synaptic elimination

Question 20

What cell adhesion molecules are needed for CNS synapse formation?

Answer 20

NCAM, SynCAM, and L1

Question 21

What presynaptic neuronal adhesion molecules are involved in CNS synapse formation? What are mutations linked to?

Answer 21

neurexin (presynaptically) and neuroligin (postsynaptically);
mutations are linked to autism disorder