Synapse Formation & Elimination

Question 1

Developmental model of Synapses?

Answer 1

the Neuromuscular Junction (NMJ)
- easy to manipulate in vivo
- culturing is much easier in vivo in comparison to peripheral synapses
- there are abundant sources of these synapses

Question 2

What is responsible for ACh clustering?

Answer 2

Agrin - a large protein that becomes trapped in the basal lamina and this directs post junctional specialisation

Question 3

What increase surface area for AChR clusters?

Answer 3

Post-junctional folds

Question 4

Synapse formation requires:

Answer 4

contact, AChR clustering, weeks to mature

Question 5

Signals for pre- and post-synaptic differentiation localised to…

Answer 5

synaptic basal lamina

Question 6

What is the basal lamina

Answer 6

A strong, fibrous, permeable matrix that acts primarily as a base on which cells in the body can grow (also links cells together and to underlying CT)

Question 7

What protein is released to initiate synapse formation once an axon has arrived at its desired location?

Answer 7

Agrin

Question 8

What is agrin a signal for?

Answer 8

post-synaptic differentiationWhat do anti-agrin antibodies do?

Question 9

What do anti-agrin antibodies do?

Answer 9

block AChR clustering

Question 10

True or False: In the NMJ, agrin secreted by the neuron is trapped by the basal lamina.

Answer 10

True

Question 11

What happens to agrin -/- mice?

Answer 11

They lack normal synapses due to a reduction in AChR clusters, and therefore die after birth due to faulty diaphragm

Question 12

Why is there inter-axonal competition for synaptic sites during development?

Answer 12

to choose the strongest synapses that’s required to last, in many cases, a lifetime

Question 13

__ does not lead to a net weakening of synaptic drive on target cells - the remaining input is the ‘best’

Answer 13

Synaptic Elimination

Question 14

At birth, multiple axons converging at the NMJ are intermingled (inter-axonal competition). By postnatal day __ , a single axon innervates the post-synaptic site.

Answer 14

15

Question 15

__ neural activity is a feature in early brain development

Answer 15

Synchronous

Question 16

As development continues, patterns of neuronal firing of motoneurons changes from synchronous to asynchronous, which leads to __

Answer 16

inter-axonal competition and synaptic elimination

Question 17

What is the irreversible competitive AChR antagonist found in snake venom?

Answer 17

Alpha-bungarotoxin (blocks transmission through AChR clusters, thereby blocking activity in postsynaptic cell)

Question 18

What is crucial for the maintenance of synapses?

Answer 18

Post-synaptic activity

Question 19

Does asynchronous neuronal firing develop before or after synapse elimination

Answer 19

before

Question 20

What is the Neurotrophic Factor Hypothesis?

Answer 20

Developing neurons compete with each other for a limited supply of a NTF provided by the target tissue i.e. the neuron that takes up the most BDNF, for example, survives

Question 21

The pro-form of BDNF binds…

Answer 21

p75 (Low Affinity)

Question 22

The mature form of BDNF binds

Answer 22

TrkB (high affinity tropomyosin-related kinase receptor)

Question 23

True or False: The pro-form of BDNF is biologically inactive

Answer 23

False - it just binds a different receptor to mBDNF

Question 24

What protein also forms a high affinity binding site with p75?

Answer 24

Sortilin

Question 25

Pro-neurotrophins may induce __

Answer 25

apoptosis

Question 26

Intracellular cleavage of proneurotrophins by the action of ..

Answer 26

furin or proconvertase

Question 27

Extracellular cleavage of proneurotrophins by the action of …

Answer 27

matrix metalloproteinase (MMP)-7 or -9

Question 28

Morpholino knock-down endogenous TrkB shows that…

Answer 28

mBDNF plays an active role in preventing synaptic retraction of the active terminals through TrkB

Question 29

What is the main NT expressed at the NMJ

Answer 29

ACh