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BMS 249 - Developmental Neurobiology > Synaptogenesis > Flashcards

Synaptogenesis Flashcards

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1
Q

How are the amount of synapses in the body altered throughout time?

A

Initially, many form, which are refined back in the adult

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2
Q

What happens when the growth cone contacts the post-synaptic target cell?

A
  • Nerve cell differentiates
  • Changes in the cell membrane on BOTH cells at the point of contact
  • Specialised structures form in the membrane to allow chemical signalling to occur
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3
Q

Do all neurons form synapses in development?

A

No

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4
Q

What determines if a synapse survives or dies back?

A

Activity-based reinforcement

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5
Q

What are plastic changes of synapses involved in?

A

Learning and memory

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6
Q

Are there differences between synapses formed in development and in regeneration?

A

Some differences and some similarities

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7
Q

What must be present in order to form functional synapses?

A
  • Correct receptors, which match the target tissue
  • Synapses at the correct location
  • Correct part of the membrane differentiating into a synapse
  • Correct number of synapses made

(Work in the correct way and in the right place, between the right neurons)

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8
Q

What is dependant development?

A

Some cell types are dependant on being innervated (synapse formation) in order to differentiate

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9
Q

Which cells are contact dependant?

A

Muscle spindles

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10
Q

Which cells are contact independant?

A

Merkel cells (touch cells)

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11
Q

What are the morphological features of synaptic specialization between an auditory endbulb and a target: Spherical Bushy Cell?

A
  • Small vesicles at the presynaptic membrane
  • Narrow cleft (filled with ECM) between pre and post synaptic membranes
  • Thickening of the postsynaptic membrane (post synaptic density)
  • ECM matrix proteins accumulate, receptor recruitment, tight junction formation (in POSTSYNAPTIC membrane)
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12
Q

When does synaptogenesis occur?

A

When axons reach their targets, which is highly variable

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13
Q

In cats, why does synaptic density increase at post-natal day 10?

A

Cat opens eyes and this drives synapse formation in the retina (need sensory inputs)

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14
Q

When does synaptic density increase in the mouse?

A

Post-natal week 1

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15
Q

What dictates synaptic sites?

A
  • Approaching growth cone communicates to the target by releasing a signal (eg. Ach when approaching a muscle target)
  • May have pre-prepared sites on the post-synaptic membrane which contain adhesion molecules
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16
Q

How can site availability for a synapse be restricted?

A

Astrocytes may cover parts of the neuron (eg. cover the cell body so that only the dendrites are free for synapse formation)

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17
Q

What happens to adhesion when a growth cone CONTACTS its target?

A

Adhesion increases between the growth cone and the post-synaptic membrane

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18
Q

What is the structure of adhesion molecules?

A

Many different adhesion molecules
Many different domains
Many contain IMMUNOGLOBULIN domain

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19
Q

What happens to adhesion when a synapse matures?

A

Adhesion molecules become localised next to the synapse

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20
Q

What is the receptor in a neuromuscular junction and what does it bind?

A

Nicotinic AchR

Binds ACh

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21
Q

When a neuromuscular junction is formed, what are the early effects?

A

1) RECEPTOR CLUSTERING:
- Diffuse distribution of receptors in the membrane become a focussed distribution

2) INCREASE TRANSCRIPTION IN CELLS RECEIVING INNERVATION:
- Increase transcription in adjacent nuclei
- Decrease transcription in nuclei further away

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22
Q

What receptors cluster in developing myotubes?

A

AchR

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23
Q

What receptors are inhibitory?

A

Glycine and GABA

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24
Q

What receptors are stimulatory?

A

Glutamate

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25
What does glycine use to cluster receptors together?
Protein called Gephyrin, which is bound to the receptors
26
Which receptor undergoes some clustering, before the neuron arrives?
AchR
27
Which axons induce receptor clustering
Motor axons
28
What induces receptor synthesis? How?
ARIA (Ach receptor-inducing activity) Increases AchR subunit mRNA (esp. e subunit, which replaces gamma subunit in a mature receptor)
29
Where is ARIA released from?
Motor neurons
30
What family is ARIA a part of?
Neuregulin family
31
Where are neuregulins found?
In the developing brain (CNS)
32
What do neuregulins do? (2 things)
Help to pattern synaptogenesis (get the right synapses in the right places, with the right strength) Increase NMDA receptors in the developing cerebellum
33
How are many different neuregulins used in synaptogenesis?
To fine tune the process
34
How is the basal lamina important in synaptogenesis? (experiment)
- Coded roadmap which can be used in regeneration - Helps to evoke clustering of receptors Experiment: - Denervated and destroyed muscle can grow back and reinvoke the formation of NMJs and receptor clustering (ECM must help to do this as the only structure left)
35
Where is Agrin purified from?
T.californica AChR clusters
36
Where is Agrin made?
In BOTH motorneurons and muscle
37
What can be used to study why AchRs cluster?
T.californica - has very high organisation in the tissue, to allow it to kill its prey by electric shocks
38
What domains does Agrin have and why?
ECM binding domain Protein binding domain For adhesion
39
What do Agrin KOs form?
Malformed NMJs
40
In the hippocampus, what happens if apply Agrin antisense mRNA?
Reduces the amount of hippocampal synapses
41
What experiment was done to see what the function of Agrin was? What did this show?
Apply antibodies to neural Agrin - stoped clustering Apply antibodies to muscle Agrin - doesn't stop clustering Show that it is the Agrin from NEURONS which induces clustering
42
Where does Agrin secreted from the nerve bind to?
MUSK (muscle-specific kinase) on the muscle
43
What is the structure of MUSK?
Has different complexes: 1) RATL (Rapsyn-associated transmembrane linker) 2) MASC (myotube-associated specificity component)
44
Where is MUSK made?
In the post-synaptic muscle target
45
Which complex on MUSK binds to AchR?
RATL
46
What happens in a MUSK KO?
Lose ability to cluster AchR
47
What is rapsin required for?
Clustering
48
What is required for intracellular signalling?
Receptor clustering + electrical activity
49
Do synapse change through development? Why?
Yes, synapses changing thought to be involved in memory
50
Why is important to have refined synaptic connections?
To produce circuits
51
What are climbing fibres and what happens to them during development?
Neuronal synapses on purkinje cells | In development: go from 4 --> 1 climbing fibre pre PC
52
What is the process of climbing fibre reorganisation?
- Initially, multiple CF innervate PC soma - One PC selected through activity, to strengthen connections with PC - This strenghtened PC, shifts its connections, from the soma, to the dendrites - Weaker connections stay around the soma - Connections around the soma are killed off - One CF which is left has multiple connections to the dendrite
53
What does the neurotransmitter choice of a neuron depend upon?
The environment of the cell body of the neuron
54
What happens when an adrenergic cell body is implanted into a cholinergic neuron site and vice versa?
Neurons switch the neurotransmitters they produce, so that the parasympatheic neuron is now adrenergic and the sympathetic neuron is now cholinergic
55
In rat sweat glands, how does the innervation change?
Changes from adrenergic to cholinergic between P7 and P21
56
What happens if transplant footpad tissue into adrenergic innervation area?
Switches innervation from cholinergic to adrenergic
57
What are 'silent synapses'?
Mature synapses (have all the machinery to work) but where there is no electrical activity (non-functional)
58
Where are 'silent synapses' found?
In NMJs and glutaminergic systems In mature and developing nervous systems
59
Which synapse is crucial for memory? What occurs at this synapse?
Glutamenergic synapse in CA1 in the hippocampus Schaffer collaterals received at this synapse, from CA3 region of the hippocampus
60
What can activate 'silent synapses'? What does this form? What is this called?
Tectanic stimulation (very high frequency stimulation) Froms a stronger synapse Long-term potentiation
61
How long does tectanic stimulation enhcance activity in a synapse for?
Minutes to years, depending upon the circuitry involved
62
How does tectanic stimulation turn on/strengthen synapses?
- Glutamate receptors in the synapse are initially blocked at resting potential, with Mg2+ - High frequency stimulation drags the Mg2+ out of the glutamate receptors - This activates the receptors and causes calcium release - Ca2+ upregulates AMPA - unblocks the synapse and makes it electrically active (no Mg2+ block)
63
What happens if synapses are not used?
They are lost
64
When does synapse formation/modification finish?
It doesn't, it goes on throughout life

BMS 249 - Developmental Neurobiology (16 decks)

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