Synapse Formation Flashcards

1
Q

What are muscles innervated by?

A

Motor neurons

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2
Q

What are the 3 cells involved in neuromuscular junction synapses?

A
  • Axon terminals
  • Muscle fibres
  • Schwann cells
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3
Q

Where do synapses happen in the muscle?

A
  • Synapses made at shallow depression in muscle
    • Sarcolemma invaginated at syapse to form deep, regular post functional folds
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4
Q

What is a post junctional fold?

A

Present at the troughs and crests:

  • at crest: loads of ACh receptors
  • at troughs: lots of voltage gated Na+ channels
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5
Q

Outline the basic process of the neuromuscular synapse.

A
  • single transmitter ACh released froma axon
  • single NT type - nicotinic AChR expressed on post synaptic membrane
  • motor neuron forms a bouton above synapse, surrounded by schawnn cell, bouton contains large number of synaptic vesicles and synaptic vesicle dockery and fusion proteins
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6
Q

Where is ACh receptor expressed?

A

On surface of muscle cell

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7
Q

How are AChR pre-patterened to the centre of muscle fibres before motor axons arrive?

A

AChR clusters are stabilised at synaptic sites whilst extra AChR is lost. Muscle secretes neurotrophic factors to promote for survival of innervating motor axons

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8
Q

How are short opening periods of the AChR achieved after motor axon innervation?

A
  • AChR made of 4 subunits: α, γ, β, δ - characterised when receptor bind to receptor and ion pore
  • After motor neuron axon is innervated, muscle fibre gets change in composition of AChR, get v short opening periods allow high level of current to flow through
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9
Q

How is expression of post-synaptic AChRs induced? (8 marks)

A
  1. Innervating motor axons secrete proteoglycan Agrin - this binds to Lrp4
  2. Agrin/Lrp4 form complex with dimers of TRK Musk - each Musk molecule is phosphorylated at tyrosine residue Y553
  3. Y553 phosphorylation recruits Dok7 adapter protein leading to its dimerization and phosphorylation
  4. Dok7 dimeriation and phos, increases Musk activity and recruits Crk/ Crk-L
  5. JNK and Rho/ Rac GTPase activation results in Rapsyn binding to AChR cluters and their stabilization
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10
Q

What do motor axons do at a potential synapse?

What does this suggest about Agrin and Musk signalling?

(4 marks)

A
  • Don’t stop growing and develop synaptic boutons at presumptive synapse
    • They express AChR
  • Suggests agrina nd musk signalling generates a muscle derived trophic molecule required for synaptic bouton formation and maturation
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11
Q

What have transgenic mice revelead the importance of Musk, Lrp4 and Dok7?

A

That they are all essential for expression of central motor neuron AChR clusters before innervation

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12
Q

Where is the only place that synapses can be made in the CNS?

A

Dendritic shaft - as they can be both inhibtory as well as excitatory

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13
Q

Name a few of the pre-synaptic proteins in the pre-synaptic zone. (4 marks)

A

Synaptic vesicle

Fusion proteins

Synaptic vesicle docking proteins

Scaffolding proteins

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14
Q

Why are post synaptic membranes electron dense?

A

High level of neurotransmitter receptors expressed and scaffolding proteins

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15
Q

What do scaffolding proteins do in the pre-synaptic zone?

A

Form structure for docking fusiom proein to bind to e.g. Piccolo (scaffolding protein)

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16
Q

What do excitatory glutamatergic synpases contain?

A

Scaffolding proteins e.g. PASD-95, and cluster NMDA and AMPA receptors and their associative signalling molecules

17
Q

What kind of molecules are in teh excitatory post-synaptic density?

A
  • Post synaptic adhesion proteins e.g. cadherins
  • Ion channels e.g. AMPA and NMDA glutamate receptors
  • Scaffolding proteins e.g. PSD-95
  • Signalling molecules e.g. CamKII
18
Q

What are the first stages in excitatory synapse development?

A
  1. Incoming growth cone releases neurotransmitter
  2. If dendrite expressed is suitable, NTRs is attracted to the axons
  3. Interaction between pre and post synaptic adhesion proteins stabilises the developing synapse and initiates synaptic maturation
19
Q

What is the second stage in excitatory synapse development?

A
  1. Prefabricated components of presynaptic active zone are transported to the zone in pre-assembled transport vesicles
  2. Vesicles deposit pre-synaptic components inot the actie zone
  3. Lots of transport vesicles associated with scaffold proteins Bassoon and Piccolo which engage with microtubule motor protein dynein
20
Q

What is the 3rd stage in excitatory synapse developement?

A
  1. Scaffolding proteins recrutied to intracellular domains of post synaptic adhesion proteins
  2. NMDA receptors inserted into post-synaptic membrane (synapses at this point non-functional even though NMDA receptors present they are gated and therefore need AMPA receptors)
  3. Post syn mem, lacks AMPA receptors so immature synapses silent
  4. So, insertion of AMPA receptors into post syn membrane (modulated by Pentraxins) produce functional synapses
21
Q

List some differences between excitatory and inhibtory synapses.

A
22
Q

Name some synaptic adhesion proteins - pre and post synaptic partners

A
23
Q

What do the 3 proto-cadherin clusters contain?

A
24
Q

What sort of tetramers are protocadherins functional as?

A

Homo and hetero tetramers

25
Q

What are protocadherins function? (2 marks)

A

To act as molecular bar codes to identify and distinguish different neuronal types. Synapses won’t fomr when the molecular bar code of hte to neurons are too similar

26
Q

As development proceeds what are synaptic connections primarily defined by?

A

Synaptic eliminations