Synaptic Transmission Flashcards

1
Q

What is the nernst equation?

A

This relates the numerical values of the concentration gradient in a half cell to the electrical gradient that balances it.

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2
Q

What is electrical synaptic transmission?

A

This is basically a mechanism for coupling/synchronizing cells to fire together. This is permitted through the flow of ions through gap junctions.

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3
Q

what is a limitation of electrical synaptic transmission, as opposed to chemical transmission.

A

1) Can’t be amplified. 2) always excitatory so you can’t get complex integration of excitatory and inhibitory synaptic inputs 3) can’t really modulate the signal (no learning and memory at electrical synapses)

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4
Q

Why is electrical synaptic transmission ineffective at the neuromuscular junction?

A

because the nerve terminal is so much smaller than the muscle fiber it innervates, it can’t provide enough current to depolarize the muscle.

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5
Q

Is electrical synaptic transmission impt in the mammalian CNS?

A

not really, pretty rare.

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6
Q

Name examples of electrical synaptic transmission.

A

escape reflexes, heart and smooth muscle, development of retina, inner ear, CNS: fear learning, emotional memory in hippocampus, contribution to the establishment of (alert) theta rhythms

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7
Q

Name the presynaptic events involved in transmitter release, from the time of the arrival of an action potential to exocytosis.

A

action potential arrives in the presynaptic terminal –> depolarization causes voltage gated calcium channels to open, calcium ions flow down their electrochemical gradient int o the cell –> binding of calcium ions to protein syanaptotagmin triggers fusion of the lipids of the vesicle and surface membranes –> opening a fusion pore through which the neurotransmitter diffuses out of the vesicle

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8
Q

Describe presynaptic events involved in cleanup operations, both outside the cell and inside the cell. Eg, for calcium.

A

Calcium –> pumped out of cell by 2 types of pump, one is driven by ATP (primary active transport), another is a sodium-calcium exchanger (antiporter; secondary active transport).. Finally, sodium-potassium pumps and calcium pumps in muscle surface membrane extrude sodium and calcium and reabsorb potassium.

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9
Q

how does tetanus toxin work?

A

selectively blocks inhibitory synaptic transmission produce powerful persistent, involuntary skeletal muscle contractions. Does this by selective cleavage of a protein component of synaptic vesicles called synaptobrevin II, and this prevents the release of neuro transmitters by the cells. Thus, it clips SNARES, and in so doing interferes with exocytosis.

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10
Q

how does botulinum toxin work?

A

blocks vesicular fusion in presynaptic cholinergic neurons, thereby preventing the release of ACh into the synaptic cleft. It does this by CLIPPING SNARE PROTEINS (synaptobrevin, syntaxin, SNAP-25, depends on the strain) and thus interfering with exocytosis

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11
Q

Name the postsynaptic events involved in synaptic transmission

A

liberated molecules of neurotransmitter bump into the postsynaptic membrane –> bind to receptors in postsynaptic membrane –> initiates postsynaptic response. Meanwhile, membrane is reinternalized (endocytosed) and refilled with neurotransmitter.

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12
Q

What is the ‘job description’ for a motor nerve terminal?

A

Every time an action potential arrives from the CNS, the nerve must secrete enough ACh to depolarize the muscle by about 30 mV. Too little and it won’t stimulate the muscle to contract, too much and the muscle fiber will only contract once.

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13
Q

Describe how the neuromuscular synapse amplifies the incoming signal in order to depolarize the muscle fiber to threshold for an action potential.

A

1) each synaptic vesicles contains several thousand ACh molecules. Each receptor that is activated, permits the flow of about 1000 positive charges into the muscle fiber. 2) synaptic terminal is bulked up – a) length of contact with muscle is extended b) has a few hundred active zones c) has tens of thousands of synaptic vesicles

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14
Q

What is the safety factor at the NM junction? Do CNS synapses have safety factors as well? Why/why not?

A

motor nerve terminal secretes the contents of a few times more than the minimum number of synaptic vesicles needed.

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15
Q

Define facilitation and synaptic depression of transmitter release. Name the underlying mechanism of each.

A

Facilitation –> during repetitive simulation, calcium ion concentration in the presynaptic terminal builds up because it can’t be cleaned up as fast, this results in increased exocytosis. So residual calcium (calcium that hasn’t been pumped out from previous action potentials) increases number of quanta secreted. Synaptic depression –> nerve terminal runs out of releasable vesicles, so number of quanta secreted decreases.

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16
Q

Describe the basic mechanism that determines whether a synapse is direct (fast) or indirect (slow). Name a typical physiological response mediated by each.

A

fast (direct) –> neurotransmitter directly gates an ion channel, which instantly changes membrane permeability. slow (indirect) –> neurotransmitter receptor protein is not an ion channel but rather a protein channel that undergoes a structural rearrangement, then G protein senses the conformational change and initiates a series of events that ultimately leads to a change in ion channel behavior. NMJ = Fast, CNS= fast or slow.

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17
Q

Describe the conductance (permeability) characteristics of the channel opened in fast excitation.

A

ACh receptor channels at the NMJ are permeable to all CATIONS. It is thus called a Non-Selective Cation channel.

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18
Q

Define the electrical “driving force.”

A

This is voltage, which is the difference in electrical potential across the cell.

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19
Q

Define the reversal potential for direct excitation.

A

Since NSC channels are nonselective to all cations, opening an infinite number of these channels would drive the muscle fiber membrane potential to a value between Ena and Ek. This is defined as the reversal potential.

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20
Q

Describe the kind of channel that is opened during fast inhibition in the CNS.

A

ionotropic, NSC channel.

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21
Q

Why is inhibition often more powerful than one might predict from the size of an individual inhibitory post-synaptic potential (IPSP)?

A

This is because he effect of an IPSP depends on the relative permeabilities of each participating ion. It depends on the ion’s equilibrium potential in relation to the resting potential. Eg. chloride.

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22
Q

Define temporal and spatial summation of postsynaptic potentials.

A

spatial summation - 2 or more different inputs (excitatory synaptic inputs) summate to drive a motor neuron to fire an action potential simultaneoulsy. temporal summation - same input is stimulated in succession.

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23
Q

Describe the 3 mechanisms for removing transmitters from synaptic clefts.

A

1) diffusion out of the cleft and into surrounding ECF 2) recyling – molecules are pumped back into the presynaptic terminal by specialized sodium-coupled cotransporters 3) destroyed (eg ACh). acetylcholine esterase cleaves ACh, producing acetate and choline.

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24
Q

What is a coincidence detector? How does the NMDA receptor work as a coincidence detector?

A

Type of receptor that require not only glutamate (to open the glumate activated gate) but also a postsynaptic action potential (to remove the mg ion). NMDA receptors also have a high permeability to calcium ions.

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25
How can activation of NMDA receptors lead to synaptic strengthening?
Through a couple different mechanisms -- 1) activation of NMDA receptors causes Ca++ influx, which triggers exocytosis of vesicles that insert additional AMPA receptors into the postsynaptic membrane. 2) can also occur presynaptically through retrograde signal from the postsynaptic cell to the presynaptic terminal. entry of calcium ions through NMDA receptor channels into the postsynaptic dendrite promotes synthesis of NO, which diffuses back across the synapse and potentiates transmitter release.
26
How might such a mechanism (synaptic strengthening as a consequence of NMDA activation) lead to behavioral associative conditioning?
conditioned stimulus is paired with unconditioned stimulus. Strong input from UCS rmakes in AP in the output cell that pops open the Mg++ ion out of the NMDA channel pore, but only at selective CS synapse, which can then activate the output cell.
27
What is LTP, what is LTD? How are they involved in learning and memory?
LTD -- with low frequency stimulation, synaptic responses become smaller and stay smaller. (mechanism probably involves retrieval of AMPA receptors from the postsynaptic membrane, which then become less sensitive to glumate secreted by the presynaptic terminal. LPD -- instead of the postsynaptic vesicle secreting transmitter, it inserts additional AMPA receptors into the postsynaptic membrane, which increases the size of glutamate-induced synaptic potentials.
28
major excitatory transmitter in the CNS
glutamate
29
major inhibitory transmitter in the CNS
GABA, which acts by increasing chloride permeability in the postsynaptic membrane.
30
nicotinic receptors
ACh receptors (also activated by nicotine) that is a NSC and produces fast synaptic potentials.
31
muscarinic receptors
ACh receptor coupled to a G protein that is indirect/slow
32
synaptic integration
summation of excitatory and inhibitory potentials in neurons
33
trigger zone
junction between cell body and the axon where action potentials always arise. also called axon hillock/initial segment
34
how does presynaptic inhibition of transmitter release work?
This occurs with inhibitory nerve terminals that synapse on other excitatory presynaptic terminals (creating a sandwich). Action potential in inhibitory terminal (#1) releases GABA, which opens chloride channels in the target presynaptic terminal. Open chloride channels reduce the number of voltage-gated Ca channels that open in response to the action potential. Net effect is to reduce neurotransmitter release. This provides a mechanism to selectively shut off certain inputs to a cell without affecting its resting membrane potential.
35
examples of deficiencys in electrical synapse transmission
charcot-marie-tooth neuropathy
36
pharmacologic means of modulating gap junctions
tonabersat and derivatives (benzopyrans) have reduced migrane episodes and seizures by modulating gap junctions between neurons and glia
37
active zone
zone in presynaptic terminals where vesicles are stored and docked. basically a group of proteins (presynaptic terminals, proteins, calcium channels, etc.) involved in this.
38
myasthenic syndrome (aka lambert-eaton syndrome)
patient's immune system makes inappropriate antibodies to presynaptic calcium channels in NMJ.
39
synaptobrevin
SNARE protein. Interacts with corresponding molecules in presynaptic membrane.
40
Synaptotagmin.
SNARE protein. Calcium sensor.
41
SNAP25
SNARE protein in presynaptic membrane that binds to synaptobrevin
42
Syntaxin
SNARE protein in presynaptic membrane that binds to synaptobrevin.
43
NSF protein
Protein that comes in and unties SNARE complex
44
Dynamin
protein responsible for pinching off vesicle during cleanup
45
Describe mechanisms for membrane retrieval
1) 'kiss and run' is the rapid mechanism. vesicle and membrane fuse briefly but remain intact (only partly fuses with membrane and then opens pore) and can be pinched off 2) vesicles collapse into the surface, then requires clathrin to be retrieved, and dynamin to pinch it off 3) surface membrane bubbles back inside as long, narrow infoldings. didn't emphasize this third mechanism.
46
most impt inhibitory neurotransmitters
GABA, but also GLYCINE.
47
most impt excitatory nuerotransmitters
ACh and glutamate
48
quantum hypothesis
neurotransmitters are released in discrete packets/quanta. 1 quanta = 1 vesicle.
49
"mini"
current created by spontaneous release of 1 vesicle
50
How can you calculate reversal potential
Nernst equation (for one ion) or Goldmann-Hodgkin-Katz equation (for multiple ions).
51
What is the driving force?
difference between reversal potential and action potential. Think about it as basically the voltage of a single channel (so specific to ion). The driving force dictates DIRECTION of ion movement.
52
what is reversal potential?
it's basically what a particular channel wants to bring the cell membrane to.
53
How is permeability for particular ions determined?
properties of the ion channel.
54
Sarin, cyclosarin, tabun
chemicals used in chemical warfare that block AChE
55
location of AChE
In the middle of the synaptic cleft.
56
end plate definition
presynaptic terminal at NMJ
57
motor unit definition
one motor neuron and all the muscle fibers attached to it.
58
how many vesicles are required to reach AP at NMJ?
about 30
59
time course for depression and facilitation
depression takes seconds to about 1 minute. facilitation takes milliseconds to less than 1 second.
60
what property do myasthenic syndrome patients experience?
facilitation. this is because antibodies to presynaptic calcium channels cause the accumulation of calcium in the synapse. This explains why they become stronger with exercise.
61
what property do myasthenia gravis patients experience?
synaptic depression. this is because repetitive firing occurs with no response, so vesicles run out. This explains why they become weaker with exercise.
62
central synapse
synapse in the CNS
63
fragile-X syndrome
Most common single gene inherited form of mental impairment. Causes increased spine length and decreased spine density. So this causes fewer synapses to innervate.
64
Other diseases affecting spine density
prion disease, AD
65
How can GABA channels be modified?
They have additional modulating binding sites such as for benzos, barbiturates, ethanol, and neurosteroids.
66
GABA reuptake mechanism
combination of reuptake and diffusion
67
What are GABA reuptake inhibitors used for?
seizures, epilepsy, convulsions, anxiety disorders, for anesthesia
68
synaptic integration
cumulative actions of synapses over a short period of time.
69
why do inhibitory synapses tend to be very powerful?
1) generally closer to the cell body (excitatory tend to be further out on dendrite) 2) reversal potential of inhibitory channels is close to the resting potential
70
shunting inhibition
reversal potential of inhibitory synapses is near the resting potential, which explains inhibitory post-synaptic potentials are so powerful.
71
Factors influencing neural integration
1) reversal potential (excitatory or inhibitory) 2) size of each synapse 3) distance of each synapse from the axon soma/hillock 4) number of excitatory vs. inhibitory synapses active 5) leakiness of the neuron (determines how long depolarization will last for since in some cells, ions leak back out more easily, which increases window of integration).
72
EPSP
change in voltage you can measure in postsynaptic cell following excitatory event
73
EPSC
Same as EPSP but measuring current rather than voltage
74
how g proteins work
neurotransmitter bind, g protein dissociates intracellularly, betasubunit induces conformational change in ion channel that opens it.
75
How do second messenger g proteins work?
Indirect synapses. Key property is that **transmitter receptor and site of action (ion channel) are separate proteins. In addition, to g protein dissociation, there is an intermediary step of activating adenylyl cyclase, which increases cAMP production, which activates a protein kinase, which then activates an ion channel.
76
How do you turn off second messenger cascades?
Either 1) phosphodiesterase, which breaks down cAMP into AMP. OR 2) protein phosphatase, which removes phosphate groups from proteins (so opposite of kinase).
77
properties of central synapses
fast or slow, excitatory or inhibitory, mostly weak, mostly don't have a safety factor, all types of transmitters, uptake main mechanism for termination, smart (information processing)
78
what is synaptic integration?
A neuron experiences cumulative depolarization or hyperpolarization due to all the synaptic activity (excitatory or inhibitory) going on at a given moment in time.
79
How do NMDA receptors strengthen synapse?
signaling cascade --> increase in postsynaptic receptor density --> same number of transmitter molecules have a larger effect (potentiation).
80
which is the more common form of synaptic transmission in the CNS?
chemical
81
what would happen if post-synaptic terminal released an excess of ACh?
muscle fiber would just twitch once, regardless of the size of the stimulus.
82
what does one MEPP represent?
spontaneous exocytosis of one vesicle.
83
what is the vesicular hypothesis?
each quantum reflects the contents of a single synaptic vesicle
84
what determines whether a synapse is excitatory or inhibitory?
This is determined entirely by the nature of the POSTSYNAPTIC RECEPTOR, in particular, the IONIC SELECTIVITY of the channel.
85
What are NSC channels permeable to?
sodium and potassium.
86
what is an advantage of a second messenger system as opposed to a directly activated channel?
1) second messengers often persist in the cytoplasm much longer than neurotransmitters in the synaptic cleft (like emotions). 2) they can also do a lot more, like activate gene expression
87
what are the impt characteristics of NMDA receptors?
1) pore is plugged by a magnesium 2) high permeability to calcium ions
88
mechanism behind silent synapses?
initially they only include NMDA receptors and NO AMPA receptors, but after they're activated, AMPA receptors are inserted into the postsynaptic membrane and the synapse begins to respond normally.