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BMS 249 - Developmental Neurobiology > Synaptogenesis > Flashcards

Synaptogenesis Flashcards

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
Q

What does glycine use to cluster receptors together?

A

Protein called Gephyrin, which is bound to the receptors

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26
Q

Which receptor undergoes some clustering, before the neuron arrives?

A

AchR

27
Q

Which axons induce receptor clustering

A

Motor axons

28
Q

What induces receptor synthesis?

How?

A

ARIA (Ach receptor-inducing activity)

Increases AchR subunit mRNA (esp. e subunit, which replaces gamma subunit in a mature receptor)

29
Q

Where is ARIA released from?

A

Motor neurons

30
Q

What family is ARIA a part of?

A

Neuregulin family

31
Q

Where are neuregulins found?

A

In the developing brain (CNS)

32
Q

What do neuregulins do? (2 things)

A

Help to pattern synaptogenesis (get the right synapses in the right places, with the right strength)

Increase NMDA receptors in the developing cerebellum

33
Q

How are many different neuregulins used in synaptogenesis?

A

To fine tune the process

34
Q

How is the basal lamina important in synaptogenesis? (experiment)

A
  • 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
Q

Where is Agrin purified from?

A

T.californica AChR clusters

36
Q

Where is Agrin made?

A

In BOTH motorneurons and muscle

37
Q

What can be used to study why AchRs cluster?

A

T.californica - has very high organisation in the tissue, to allow it to kill its prey by electric shocks

38
Q

What domains does Agrin have and why?

A

ECM binding domain
Protein binding domain

For adhesion

39
Q

What do Agrin KOs form?

A

Malformed NMJs

40
Q

In the hippocampus, what happens if apply Agrin antisense mRNA?

A

Reduces the amount of hippocampal synapses

41
Q

What experiment was done to see what the function of Agrin was?

What did this show?

A

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
Q

Where does Agrin secreted from the nerve bind to?

A

MUSK (muscle-specific kinase) on the muscle

43
Q

What is the structure of MUSK?

A

Has different complexes:
1) RATL (Rapsyn-associated transmembrane linker)

2) MASC (myotube-associated specificity component)

44
Q

Where is MUSK made?

A

In the post-synaptic muscle target

45
Q

Which complex on MUSK binds to AchR?

A

RATL

46
Q

What happens in a MUSK KO?

A

Lose ability to cluster AchR

47
Q

What is rapsin required for?

A

Clustering

48
Q

What is required for intracellular signalling?

A

Receptor clustering + electrical activity

49
Q

Do synapse change through development? Why?

A

Yes, synapses changing thought to be involved in memory

50
Q

Why is important to have refined synaptic connections?

A

To produce circuits

51
Q

What are climbing fibres and what happens to them during development?

A

Neuronal synapses on purkinje cells

In development: go from 4 –> 1 climbing fibre pre PC

52
Q

What is the process of climbing fibre reorganisation?

A
  • 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
Q

What does the neurotransmitter choice of a neuron depend upon?

A

The environment of the cell body of the neuron

54
Q

What happens when an adrenergic cell body is implanted into a cholinergic neuron site and vice versa?

A

Neurons switch the neurotransmitters they produce, so that the parasympatheic neuron is now adrenergic and the sympathetic neuron is now cholinergic

55
Q

In rat sweat glands, how does the innervation change?

A

Changes from adrenergic to cholinergic between P7 and P21

56
Q

What happens if transplant footpad tissue into adrenergic innervation area?

A

Switches innervation from cholinergic to adrenergic

57
Q

What are ‘silent synapses’?

A

Mature synapses (have all the machinery to work) but where there is no electrical activity (non-functional)

58
Q

Where are ‘silent synapses’ found?

A

In NMJs and glutaminergic systems

In mature and developing nervous systems

59
Q

Which synapse is crucial for memory?

What occurs at this synapse?

A

Glutamenergic synapse in CA1 in the hippocampus

Schaffer collaterals received at this synapse, from CA3 region of the hippocampus

60
Q

What can activate ‘silent synapses’?

What does this form?

What is this called?

A

Tectanic stimulation (very high frequency stimulation)

Froms a stronger synapse

Long-term potentiation

61
Q

How long does tectanic stimulation enhcance activity in a synapse for?

A

Minutes to years, depending upon the circuitry involved

62
Q

How does tectanic stimulation turn on/strengthen synapses?

A
  • 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
Q

What happens if synapses are not used?

A

They are lost

64
Q

When does synapse formation/modification finish?

A

It doesn’t, it goes on throughout life

BMS 249 - Developmental Neurobiology (16 decks)

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