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+ BIOL 371 > Lecture 9: Synaptic Transmission > Flashcards

Lecture 9: Synaptic Transmission Flashcards

1
Q

What are electrical synapses?

A

specialized ‘electrical junctions’ that allow flow of electrotonic current directly from one neuron to another

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2
Q

What are chemical synapses?

A

have no direct contact between neuron membranes – a chemical messenger bridges the gap (or cleft) between the cells

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3
Q

How are electrical synapses formed?

A

when the two opposing cell membranes both express connexin hemichannels – when aligned, these form large diameter (1nm) cross-cell pores called gap junctions

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4
Q

What is the function of electrical synapses?

A

allow rapid, bidirectional transfer of ions

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5
Q

What are electrical synapses large enough to transfer?

A

many cellular second messenger molecules, and other small(ish) molecules, including some dyes

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6
Q

What do chemical synapses act via?

A

via rapid, spatiotemporally precise exocytosis of synaptic vesicles containing neurotransmitter molecules – triggered in response to electrical activity in the presynaptic cell, and occurs very rapidly, but with high precision

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7
Q

Is vesicle exocytosis metabolically sustainable away from the cell body?

A

yes – synaptic vesicles and neurotransmitter molecules are recycled at the axon terminal so they don’t rely on transport down the axon to keep functioning

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8
Q

Is synaptic transmission tightly coupled to electrical activity? What does this mean?

A

yes – this means it is…

  • rapid (very short delay)
  • reliable (transmitter is typically only released when electrical activity has occurred – but there are a few exceptions)
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9
Q

Is chemical synaptic transmission modifiable?

A

yes – plasticity: many steps in the process of transmitter release (and transmitter detection) can be regulated by cellular activity

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10
Q

What is the presynaptic compartment?

A

releases neurotransmitter

typically the axon terminal – compartment of the neuron which is biochemically distinct from the rest of the axon

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11
Q

What is a synaptic vesicle?

A

contain neurotransmitter to be released

recycled (reformed) in the area surrounding the active zone

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12
Q

What is the active zone?

A

specialized part of the axon terminal membrane where transmitter release occurs

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13
Q

What is the synaptic cleft?

A

extracellular space crossed by neurotransmitter

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14
Q

What is the postsynaptic compartment?

A

receives neurotransmitter

  • typically located on dendrite or soma
  • its specializations depend on what type of synapse it is (excitatory, inhibitory or modulatory)
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15
Q

What is the postsynaptic density?

A

specialized part of the membrane where neurotransmitter receptors are located

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16
Q

What molecules/proteins are required for transmitter loading? (2)

A
  • transmitter transporters

- proton pump

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17
Q

What molecules/proteins are required for mobilization? (1)

A

synapsins

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18
Q

What molecules/proteins are required for docking? (1)

A

SNAREs

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19
Q

What molecules/proteins are required for priming? (1)

A

SNAREs

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20
Q

What molecules/proteins are required for fusion? (3)

A
  • synaptotagmins
  • SNAREs
  • VG Ca-channels
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21
Q

What molecules/proteins are required for coating? (2)

A
  • clathrin

- synaptotagmins

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22
Q

What molecules/proteins are required for budding? (3)

A
  • dynamin
  • clathrin
  • actin
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23
Q

What molecules/proteins are required for uncoating? (1)

A

clathrin

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24
Q

What is a neuromuscular junction?

A

synapse between somatic motor neuron and muscle cell (also called muscle fibre)

25
Q

What is a neuromuscular junction similar to?

A

quite similar to excitatory synapses in the CNS

26
Q

What is the terminal bouton?

A

(pre-synaptic) axon terminal of muscle synapse

27
Q

What is the motor end plate (MEP)?

A

postsynaptic density in a muscle synapse

28
Q

What is end plate potential (EPP)?

A

excitatory postsynaptic potential in a muscle synapse

29
Q

What do many synapses in vertebrate peripheral nervous system, including neuromuscular junction, use as their neurotransmitter?

A

acetylcholine (small organic ion)

30
Q

What does synaptic transmission involve?

A

chemical messengers (neurotransmitters) released into extracellular space

31
Q

What could affect ACh signalling?

A

any naturally occurring toxins and venoms

32
Q

What are the pros of muscle synapses (NMJs)? (4)

A
  • accessibility – PNS not CNS
  • size – muscle fibres are large cells, suited for voltage clamp experiments
  • simplicity – there is only ever one synapse per vertebrate muscle fibre
  • pre-studied – ACh (neurotransmitter) was known, as were naturally occurring drugs that could enhance or block its activity
33
Q

What are the cons of muscle synapses (NMJs)? (2)

A
  • no inhibition – one excitatory synapse per fibre means only one kind of synapse can be investigated with this model system
  • TRADE-OFF: contractions – unlike neurons, muscle cells MOVE when they’re excited (this is terrible for electrode recordings)
34
Q

What are the steps in the life of a synaptic vesicle?

A
  1. fusion with the axon membrane
  2. reforming from the membrane
  3. filling with neurotransmitter
  4. storing till it is needed
35
Q

What are the steps at the active zone that occur before vesicle fusion?

A
  • docking

- priming

36
Q

What is docking?

A

process of tethering a free synaptic vesicle to the active zone

37
Q

What is priming?

A

process of bringing a docked vesicle very close to the active zone membrane

38
Q

What is fusion?

A

exocytosis of the vesicle by fusion with the active zone membrane and release of its neurotransmitter into the synaptic cleft

39
Q

What stages are SNARE proteins key participants in?

A
  • docking
  • priming
  • fusion
40
Q

Which SNARE proteins are involved in the docking, priming and fusion stages? (3)

A
  • synaptobrevin: vesicle bound v-SNARE
  • syntaxin: terminal-bound t-SNARE
  • SNAP-25: terminal-bound t-SNARE
41
Q

What is the key process that occurs in vesicle docking?

A

formation of SNARE complex

42
Q

How is SNARE complex formed?

A

when a vesicle (carrying synaptobrevin) is brought close to an active zone which contains SNAP-25 and syntaxin – make specific, relatively stable associations with each other

43
Q

What must typical EPP smoothly graded EPP in normal conditions be generated by?

A

many quanta occurring at the same time

44
Q

What is quantal synaptic transmission due to? What is the mechanism that means these responses are quantal?

A

neurotransmitter being released in equal-sized packets

each quantum represents neurotransmitter somehow being released in equally sized amounts (presynaptic)

45
Q

What are quanta?

A

equal-sized packets

46
Q

What do quanta correspond to?

A

synaptic vesicles, which fuse with axonal membrane (exocytosis), releasing their contents into the synaptic cleft

47
Q

How are neurotransmitters released?

A

released from presynaptic axon terminal in equal-sized packets (aka quanta)

48
Q

What are some observations about the relationship between Ca and neurotransmitter release?

A
  • Ca2+ must be present in extracellular fluid for stimulated release to occur at all
  • to induce neurotransmitter release, [Ca2+]o must be present at the exact time of axonal membrane depolarization (not before or after), even though vesicle fusion happens after a delay
  • [Ca2+]o has a strong effect on the number of quanta released – release is proportional to [Ca++]o^4

these observations can be explained by: voltage-gated Ca2+ channels (VGCCs)

49
Q

What do voltage-gated Ca2+ channels (VGCCs) open in response to?

A

depolarization from the AP reaching the axon terminal

50
Q

Where are voltage-gated Ca2+ channels (VGCCs) enriched?

A

subtype of VGCCs (known as ’N-type’) are specifically enriched in active zone membrane of axon terminals

51
Q

Why is the presynaptic AP not changed/barely changed by the Ca2+ chelation?

A

because VGCCs (and thus calcium currents) are only found in a very restricted subcompartment of the axon terminal (the active zone)

(release Ca2+ only around active zone)

52
Q

What does priming involve?

A

stabilization of SNARE complexes by many additional proteins

53
Q

What happens once a synaptic vesicle is docked by a SNARE complex?

A

many other active zone and axon terminal proteins also join and bind, increasing the complex’s complexity

54
Q

What functions do support (non-SNARE) proteins enable (during priming)?

A

(assembly of support protein complexes)

  • stabilization of the association between SNAREs
  • positioning the vesicle-SNARE complex near VGCCs
  • reinforcement, bringing the vesicle close (but not too close) to the membrane
  • sites for regulation of fusion by intracellular signal cascades (ie. kinases)
55
Q

What is synaptotagmin (Syt)?

A

fast Ca2+ sensor that catalyzes synaptic vesicle fusion

can bind Ca2+ ions – binding causes the whole Syt protein to change its conformation (ie. fold into a different shape)

56
Q

What does synaptotagmin do?

A

binds to calcium and its interactions with SNARE proteins catalyze fusion

  1. when a vesicle is docked and primed, synaptotagmin (vesicle protein) physically interacts with SNARE complex
  2. Ca2+ binding to synaptotagmin causes it to change shape
  3. movement of Syt forces v-SNARE and t-SNAREs to roll up more tightly, bringing the two membranes together – this opens a path for neurotransmitter release from the vesicle
57
Q

Synaptic transmission in a chemical synapse is quantal. What does this mean?

A

equal-sized packets of neurotransmitter are released in response to APs in presynaptic neuron due to fusion of synaptic vesicles with axon terminal membrane

58
Q

Synaptic release cannot occur without what?

A

calcium

critical link between terminal depolarization and vesicle fusion is influx of calcium through voltage-gated calcium channels in axon terminal

+ BIOL 371 (22 decks)

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