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Cellular Neuroscience > Synaptic Transmission > Flashcards

Synaptic Transmission Flashcards

1
Q

Electrical synapses (gap junctions) allow

A
  1. very fast, bidirectional communication between cells
    → useful to generate rhythms (e.g. for breathing) and
    oscillations (e.g. interneuron networks).
  2. exchange of small molecules like ATP, cAMP, sugars
    → relevant for large networks of glial cells that control
    neuronal metabolism
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2
Q

Function of Electrical Synapes - Gap Junctions

A
  • Allow for direct electrical communication between cells
  • Allow for chemical communication between cells, through the transmission of small second messengers, such as inositol triphosphate (IP3) and calcium (Ca2+)
  • Metabolic coupling
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3
Q

Chemical synapses

A

Translating an
electrical signal into a
chemical signal and
right back into an
electrical signal

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4
Q

The most common type is contact between

A

an axon terminal and a dendritic, somatic, or axonal domain

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5
Q

The Neuromuscular junction (NMJ)

A

Large postsynaptic cell
* One axon (but about 100 synapses !)
per muscle cell
* Highly reliable
– Most pre-synaptic action potentials lead
to a post-synaptic action potential
* Chemical signaling is simple
– Only one type of ion channel

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6
Q

END PLATE POTENTIAL (EPP)

A

Stimulation of the motor fiber
generates a synaptic potential in the post-synaptic muscle cell.

~40-50mV amplitude

Action potentials synchronize the release of many transmitter quanta

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7
Q

Miniature End Plate Potentials (MEPPs)

A

very small (miniature) potentials (~1 mV) occur even in the absence of stimulation

Eliminated in instances with redued extracellular Ca2+

EPPs are multiples of MEPPs

(Spontaneous) Neurotransmitter release occurs in quantal packets

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8
Q

Quantal release theory

Key variables that characterize quantal (vesicular) release:

A
  • the number of release sites (N)
  • the probability of a quantal release (p)
  • the size of the quantal response (q)
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9
Q

Quantal analysis

A

the distribution of amplitudes of
the postsynaptic response can be
fitted to a binominal distribution
→ From this, the best-fitting values of N, p, and q can be extracted

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10
Q

Morphological correlates of Katz’s variables

the number of release sites (N)

A

number of active zones/synapses

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11
Q

Morphological correlates of Katz’s variables

the probability of a quantal release (p)

A

number of docked vesicles

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12
Q

Morphological correlates of Katz’s variables

the size of the quantal response (q)

A

single vesicle and/or the response to a single vesicle (receptor sensitivity)

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13
Q

____is required for transmitter release (influences the probability of release)

A

Calcium

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14
Q

Presynaptic action potentials open

A

voltage-gated Ca2+ channels.

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15
Q

Ca2+ allows vesicles

A

to fuse
with the membrane

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16
Q

2-fold increase in Ca2+ can

A

increase
transmitter release 16-fold

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17
Q

Infusion of a
Ca2+ chelator such as BAPTA

A

reduces Ca2+
release

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18
Q

Action-potential triggers

A

Ca2+ influx into presynaptic terminal via voltage-gated Ca2+ channels (N- and/or P/Q type)

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19
Q

In the active zone, Ca2+ currents are

A

10x larger
than elsewhere.

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20
Q

In the active zone, Ca2+ can rise

A

1000-fold (to ~100 µM)

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21
Q

SNAREs (SNAp REceptors)

A

group of proteins that promote
fusion of the vesicle and presynaptic membrane.

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22
Q

Steps involved in vesicle release and recycling

A
  1. Trafficking
  2. Tethering
  3. Docking and Priming
  4. Fusion
  5. Endocytosis
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23
Q

Trafficking

A

target vesicles to
the active zone

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24
Q

Tethering

A

restrain vesicles in reserve pool

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25
Q

Docking and priming

A

vesicles to active zone

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26
Q

Fusion AKA

A

exocytosis

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27
Q

Endocytosis

A

retrieve fused
membrane (recycling)

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28
Q

4-AP blocks K+ channels and prolongs the
action potential and thus

A

tincreases the
amount of Ca2+ that can enter
→ leads to more quanta released per AP
→ Correlates perfectly with number of fused vesicles counted in EM

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29
Q

The fusion of a transport vesicle with its target
involves 2 types of events:

A

The transport vesicle must recognize the
correct target membrane.
* Second, the vesicle and target membranes must fuse,
so that the content of the vesicle can be delivered to the target organelle (within the cell) or into the synaptic cleft.

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30
Q

The SNARE hypothesis describes

A

vesicle fusion via the interaction between specific
pairs of transmembrane proteins, called SNARES
(SNAP [Soluble NSF Attachment Protein] Receptor)

31
Q

Two (main) types of SNAREs

A

vesicle or v-SNAREs (or R-SNAREs),

target or t-SNAREs (or Q-SNARES)

32
Q

vesicle or v-SNAREs (or R-SNAREs)

A

incorporated into the membranes of transport
vesicles during budding

33
Q

Example of a v-SNARE

A
  • Synaptobrevin sits in the vesicle membrane
34
Q

target or t-SNAREs (or Q-SNARES)

A

located in the target membranes

35
Q

Examples of t-SNAREs

A
  • Syntaxin and SNAP-25 are anchored in the presynaptic membrane (T-SNAREs)
36
Q

Calcium sensor (not a SNARE) involved in Exocytosis

A

Synaptotagmin

or VAMP (vesicle associated membrane protein)

37
Q

Functions of Synaptotagmin-1

A

Calcium Sensor
– Releases clamp on release, or facilitates release.

Involved in docking and
vesicle fusion via
interaction with βneurexin or SNAP-25

Also aids in recycling
– binds clathrin

38
Q

Neurexins

A

interaction with synaptotagmin
leads to fusion

39
Q

The SNARE complex binds

A

directly to N-type Ca++ channels

40
Q

Two neurotoxins that effect SNAREs

A

Botulinum neurotoxin and Tetanus neurotoxin

41
Q

Botulinum neurotoxin

A

cleaves SNARE proteins

42
Q

Tetanus neurotoxin

A

cleaves Synaptobrevin

43
Q

The “classic” synaptic vesicle cycle
Duration

A

~ 1 min

44
Q

Two key proteins for Endocytosis

A
  • Clathrin
  • Dynamin
45
Q

clathrin

A

forms coated pits by curving the membrane

46
Q

dynamin

A

pinches of coated vesicle

47
Q

Synaptotagmin I is involved in

A

both sides of the vesicle cycle.
Synaptotagmin serves as anchor for AP2.
Clathrin attaches to AP2 or synaptotagmin itself

48
Q

Four different modes of endocytosis

A
  1. “kiss and run”
  2. Clathrin-mediated
  3. Bulk endocytosis
  4. “Ultrafast”
49
Q

Duration of “kiss and run” endocytosis

A

1 sec

50
Q

Duration of Clathrin-mediated endocytosis

A

tens of seconds

51
Q

Duration of Bulk endocytosis

A

tens of seconds, requires strong stimulation

52
Q

Duration of “Ultrafast” endocytosis

A

50-100 ms

53
Q

Function of Synapsin

A

keeps vesicles tethered in the
reserve pool
* cross-links vesicles to
cytoskeletal filaments (f-actin)

54
Q

Synapsin is regulated by

A

Ca2+/Calmodulin-dependent kinase (CaMKII) and PKA

55
Q

Phosphorylation of Synapsin

A

frees
vesicles to move.

56
Q

Rab proteins

(members of the Ras superfamily of G-proteins)

A

Small GTP-binding protein

mark transport vesicles
* interact with v-SNAREs to initiate fusion

57
Q

Rab GTPases regulate

A

many steps of membrane traffic, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion

58
Q

more than __ different Rab proteins are involved in vesicle transport

A

60

59
Q

Neurexins (NRXN) are

A

presynaptic cell adhesion proteins.

The intracellular portion of NRXN interacts with SNAREs, while
their extracellular domain interacts with proteins in the
synaptic cleft, most notably neuroligin.

60
Q

Neuroligin 1 (NLGN1) is

A

enriched at excitatory
synapses

61
Q

NLGN2 is

A

enriched
at inhibitory, dopaminergic
and cholinergic synapses

62
Q

NLGN3 is

A

found at both
excitatory and inhibitory
synapses,

63
Q

Neurexin and neuroligin

A

“shake hands,” resulting in the
production of a synapse

Neurexin (presynaptic); Neuroligin (postsynaptic)

64
Q

An EPSP has a reversal potential more

A

positive than the AP threshold

65
Q

an IPSP has a reversal potential more

A

negative than threshold

66
Q

Post-synaptic responses

Excitatory Input

A
  • often glutamate or ACh
  • permeable to both Na+ and K+
67
Q

Post-synaptic responses

Inhibitory Input

A
  • usually GABA
  • permeable to Cl-
68
Q

Direction of post-synaptic potential determined by:

A
  • The ionic identity
  • The equilibrium (reversal) potential of that ion
69
Q

Two types of post-synaptic receptors

A
  • Ionotropic
  • Metabotropic
70
Q

Ionotropic Receptors

A

ligand-gated channels

→ receptor IS channel;
immediate conductance change

71
Q

Metabotropic receptors

A

G-protein-coupled receptors

→ receptor modulates channel, or other
intracellular effects; delayed, longer lasting response

72
Q

Binding of ligand (e.g. ACh) to receptor has

A

similar effects as changes in membrane potential on voltage-gated channels.

73
Q

The reversal potential can be used to

A

determine which ions flow
during synaptic currents

74
Q

Because under physiological conditions the
driving force for Na+
is much higher,
activation of the receptor typically results in

A

an inward current and an EPSP

Cellular Neuroscience (10 decks)

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