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Neurobiology of the synapse > Molecular mechanisms of synaptic transmssions > Flashcards

Molecular mechanisms of synaptic transmssions Flashcards

1
Q

The amplitude of evoked resposnses consists of

A

Multiple quanta

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2
Q

The mini events represent a single synaptic vesicle____________with the presyanotic plasma membrane and releasingn neurotransmitter

A

Fusion

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3
Q

The quantal content formula indicates __________________________

A

how many quanta is released

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4
Q

End plate potentials are dependent on ____________________ _________ _______________

A

External Ca concentrations

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5
Q

What does lower Ca concentration lead to and what does higher Ca concentration lead to?

A

Lower external Ca concentration leads to smaller end plate potentials or smaller neurotransmitter release

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6
Q

what doesnt change when the external Ca concnetrations are varied?

A

The amplitude of mini end plate potentials .

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7
Q

Evoked response is dependent on ___________________________________and spontaneous reponse is ____________________ on external Ca

A

External Ca concentrations, not dependent

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8
Q

What are the different categories of synaptic transmission?

A

• Synchronous evoked release: the Action potential results in fast synchronous evoked release

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9
Q

Describe synaptic transmission

A

• An action potential invades a presynaptic terminal

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10
Q

What are the three process that govern neurotransmitter release?

A

• Localized Ca influx

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11
Q

What are the different neurotransmitter release machinery

A

Synaptic vesicle fusion machinery

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12
Q

Describe the steps to Ca2+ triggered synaptic fusion

A

• Synaptic vesicles localized near the presynaptic active zone

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13
Q

What are the 4 mechanisms that are critical for synchronous release

A
  1. a nerve terminal needs to generate and maintain a pool of redly releasable vesicles that can quickly be exocytosed upon Ca entry.
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14
Q

List some Presyanptic proteins

A

• SNARES (synaptobrevin, SNAP 25, syntaxin)

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15
Q

What are SNARE motifs and a transmembrane domain?

A

SNARE motifs allow for proteins to interact with each other.

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16
Q

Why is synaptobrevin a syanaptic vesicle protein rather than a plasma membrane protein?

A

Since synaptobrevin has the transmembrane domain on its membrane synaptobrevin is able to attach itself to the synaptic vesicle

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17
Q

Why are SNAP 25 and syntaxin found on the plasma membrane

A

Because their transmembrane is on the presynaptic plasma membrane.

18
Q

What do Botulinum toxins do?

A

Cleave SNARE proteins, and prevent them from forming a SNARE complex (SNARES are important for neurotransmitter release)

19
Q

What botulinum toxins are synaptobrevin, SNAP 25 and syntaxin cleaves by?

A

Synaptobrevin is cleaved by: BoNT/F, D, B, and G

20
Q

what is the result of knocking out synaptobrevin 2 in mice?

A

Removing synaptobrevin 2 results in a severe decrease in neurotransmission because it leads to less frequency of synaptic vesicles fusing. We also see a reduction in evoked and spontaneous neurotransmission but the effect is worse for evoked transmission. Spontaneous neurotransmission is still present.

21
Q

what is the result of knocking out SNAP 25 in mice?

A

There is a severe reduction in evoked neurotransmission release than spontaneous release. Spontaneous neurotransmission is still present.

22
Q

what is the result of knocking out syntaxin in mice?

A

There is a severe reduction in evoked neurotransmitter release. Spontaneous neurotransmission is still present but it is less than what is present in synaptobrevin 2 and SNAP 25.

23
Q

What SNARE proteins form the SNARE complex

A

Synaptobrevin, Syntaxin and SNAP 25

24
Q

What proteins are critical for dissassebling the SNARE complex?

A

NSF and a-SNAP

25
Q

What are SNARE chaperones and what is their purpose?

A

CSP and synucleins can bind to various SNARE proteins and act as SNARE chaperones and are important for folding and unfolding these proteins. And they can also help prevent neurodegeneration

26
Q

What will happen if you remove synuclein ?

A

We will be inhibiting the SNARE complex resulting in less SNARE complex assembly

27
Q

Describe the Munc-18 protein

A

• Munc-18 binds to syntaxin which is a SNARE protein found on the plasma membrane

28
Q

How does Mun-18 bind to the closed and open conformations of syntaxin 1

A

• Munc-18 binds to syntaxin-1 when it was in the closed conformation where it is not able to bind to other SNARE proteins

29
Q

Membrane fusion requires two conformational transitions

A
  1. Switch from closed to open Syntaxin 1A, both which are complexed to Munc-18
30
Q

Describe the Domain and structure of Ca binidng on Synaptotagmin 1 which was found to be molecule x

A

We can have this transmembrane domain on synaptotagmin 1 which allows it to be on this synaptic vesicle membrane and we have 2 Ca binding domains called C2A and C2B and these two domains can bind to 5 Ca ion.

31
Q

Does Ca binding to synaptotagmin affinity affect neurotransmissiom?

A

• Looking at one mutant that had a higher affinity for Ca by mutating the binding domains of synaptotagmin (these have a larger amount of evoked neurotransmission)

32
Q

Do all synaptotagmins function the same?

A

Synaptotagmin 1 2 and 9 can act as Ca sensors for evoked synchronous neurotransmitter release

33
Q

reseach syggests that ________________________________is a Ca sensor for asynchronous neurotransmitter release

A

synaptotagmin 7

34
Q

Describe all the synaptotagmins and what where they are important?

A

• For fast synchronous neurotransmission synaptotagmin 1,2 and 9 are Ca sensors

35
Q

Describe Doc2b and why it is important

A

• Dco2b is another Ca binding protein; knocking it has no effect on evoked neurotransmission. But if we look at spontaneous neurotransmission we see that the frequency of these events is severely reduced in the absence of Doc2b.

36
Q

Describe Complexin and why it is important

A

• Binds to Snare protein/complexes

37
Q

How does complexin work as a Clamp and an activator?

A

• For complexin to act as an activator for evoked neurotransmitter it needs to bind to SNARE proteins

38
Q

describe complexins shape

A

• Complexin has a helix that allows it to bind to SNARE proteins

39
Q

what does complexin prevent while acting as a clamp

A

excessive spontaneous neurotransmission

40
Q

Ca triggered neurotransmitter release

A

• Need the docking step and partial assembly of snare complex

Neurobiology of the synapse (9 decks)

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