Deck 3: Signaling Across Synapses

Question 1

The efficacy of synaptic transmission can change. What best represents synaptic facilitation?
(a) A long-term increase in the number of synaptic contacts onto a postsynaptic neuron
(b) An increase in the postsynaptic response to successive presynaptic action potentials
(c) A decrease in the postsynaptic response to successive presynaptic action potentials
(d) A decrease in the amplitude of the presynaptic action potential

Answer 1

(A)
is not the best answer. Both (b) Synaptic facilitation is an increase in the postsynaptic response, or EPSP to successive action potentials in the presynaptic neuron (choice b). Facilitation is not a long-term change in synaptic strength, so choice (c) and (d) are incorrect as facilitation is an increase in the response, not a decrease.

Question 2

Myasthenia gravis is an autoimmune neuromuscular disease that results in muscle weakness caused by circulating antibodies that block acetylcholine receptors. People with the disease are treated with acetylcholinesterase (AChase) inhibitors or immunosuppressants. Why do AChase inhibitors work?

Answer 2

AChase breaks down and inactivates ACh once it is released into the synaptic cleft. In myasthenia gravis some of the receptors are blocked so increasing the amount of ACh in the cleft increases the probability that the transmitter can bind to the few receptors that are there.

Question 3

Why do you think there are so many types of presynaptic proteins involved in neurotransmitter release?

Answer 3

This is a thought question with many possible answers. Reasons could include regulation of neurotransmitter release. Neurotransmission should occur when it is needed. If it occurs at other times this can lead to incorrect information transfer. Neurotransmission must be tightly regulated, but also be able to be modified as the activity of the neuron must change frequently and rapidly depending on the current state of the neuron. Many of the proteins are there to make sure everything is in the right place. For example, some proteins make sure vesicles are located next to Ca²⁺ channels to make sure synaptic transmission is efficient.

Question 4

What are the two major/most common neurotransmitters in the vertebrate CNS?
(a) GABA and acetylcholine
(b) Glycine and acetylcholine
(c) GABA and glutamate
(d) GABA and glycine

Question 5

Describe, in general terms, experiments that show that Ca²⁺ is both necessary and sufficient for neurotransmitter release. Start with the assumption that you are recording from the squid giant synapse in which you can stimulate the presynaptic neuron and record the response in the postsynaptic neuron. State which experiment shows necessity and which shows sufficiency.

Question 6

A series of critical experiments showed the properties of chemical synaptic transmission at the neuromuscular junction. One of these is shown in Figure Q3-1 in which the voltage across the membrane was recorded with an intracellular electrode. Figure Q3-1
A. What happened when the motor axon was stimulated?
B. The investigators then applied ACh to the muscle via iontophoresis in the presence of TTX. Why did they use TTX?
C. The elicited response of ACh iontophoresis was similar to nerve stimulation. What did this tell the investigators?

Question 7

What mechanisms are used to move neurotransmitter back into vesicles? Select all that apply.
(a) A Na⁺ chemical gradient
(b) A proton gradient
(c) ATP
(d) A co-transporter

Question 8

Syt1 point mutation is a point mutation in synaptotagmin-1. How did the experiment shown in Figure Q3-12 show that synaptotagmin was probably the Ca²⁺ sensor? Figure Q3-12
B. What would the synaptotagmin-1 mutant response look like if synaptotagmin was not the Ca²⁺ sensor?

Question 9

Put the following in the correct order.
A. Neurotransmitter release
B. Ca²⁺ entry into the presynaptic terminal
C. Axonal action potential
D. Fusion of synaptic vesicle with the presynaptic plasma membrane
E. Opening of voltage-gated Ca²⁺ channels
F. Depolarization of the presynaptic terminal

Question 10

Figure Q3-6 is from an experiment that helped show that neurotransmitter release is triggered by presynaptic Ca²⁺. In panel A, the presynaptic membrane potential was clamped at -25mV. Figure Q3-6
A. How did they know Ca²⁺ entered the presynaptic neuron?
B. What happened in the postsynaptic neuron?
C. In panel B, the presynaptic membrane potential was clamped at -50mV. Why was there no net current during the presynaptic depolarization?
D. Why was there a current after the presynaptic potential was clamped back to -70mV?
E. What happened to the delay in postsynaptic current with the +50mV presynaptic depolarization?

Question 11

The presynaptic active zone must line-up with the postsynaptic density. What is one molecular mechanism that contributes to this alignment?

Question 12

Which protein is the Ca²⁺ sensor in synaptic transmission?
(a) Synapsin
(b) Munc18
(c) Synaptotagmin
(d) Synaptobrevin

Question 13

Flies with the Shibire mutant become paralyzed at high temperatures as this destabilizes dynamin. Why would this result in paralysis? Select all that apply.
(a) Actin-myosin is disrupted in muscles and they cannot contract.
(b) Vesicle release is blocked.
(c) Vesicle recycling is blocked.
(d) Synaptic vesicles are depleted in the presynaptic terminal.

Question 14

What mechanisms are used to clear neurotransmitters from the synaptic cleft? Select all that apply.
(a) Degradation by enzymes
(b) Reuptake by co-transporters
(c) Transporters on glia
(d) Diffusion

Question 15

What is the current known role of complexin in synaptic transmission?
(a) Complexin makes sure vesicles are near Ca²⁺ channels.
(b) Complexin binds vesicles to scaffolding proteins in the presynaptic membrane.
(c) Complexin clamps the SNARE complex in an intermediate step prior to vesicle fusion.
(d) Complexin is required for presynaptic Ca²⁺ channels to open.

Question 16

What is a miniature end-plate potential (mEPP)? Select all that apply.
(a) The change in postsynaptic potential at a very small muscle
(b) Spontaneous postsynaptic responses in the absence of a presynaptic action potential
(c) Small postsynaptic responses of a unitary size, or multiples of that size
(d) The change in postsynaptic potential to a very small action potential

Question 17

Figure Q3-4 documents the quantal release of neurotransmitter. Figure Q3-4
A. The investigators stimulated the nerve in low-Ca²⁺ and high-Mg²⁺ saline so that they had many failures with nerve stimulation. Why was the presence of failures so important?
B. In the top trace, there were three motor nerve stimulations that occurred at the arrow. Why is the flat trace flat and, based on what we know now, what is the reason that the other two traces are multiples of each other?
C. The investigators compared the evoked EPPs in low Ca²⁺/high Mg²⁺ saline to spontaneous EPPs (mEPP). What did they find (see figures on the right) and what did they conclude?
D. Based on the findings in this figure, what did they conclude about transmitter release in an evoked EPP in normal saline?

Question 18

What is quantal release of neurotransmitter?
(a) Release of neurotransmitter in discrete units
(b) Release of one neurotransmitter molecule at a time
(c) Release of transmitter onto extrasynaptic receptors

Question 19

What are the three main SNARE proteins?
(a) Synapsin, SNAP-25, synaptotagmin
(b) Synapsin, synaptobrevin and synaptotagmin
(c) SNAP-25, syntaxin and synaptobrevin
(d) SNAP-25, synaptotagmin, synaptobrevin

Question 20

True or False: When a depolarization occurs in the presynaptic terminal and Ca²⁺ channels open there is a large global rise in Ca²⁺ concentration. Defend your answer.

Question 21

Figure Q3-34 shows an I-V plot for the NMDA receptor in the presence of external Mg²⁺. What would the curve look like if Mg²⁺ were removed from the extracellular media and why? Figure Q3-34

Question 22

If you stimulate a glutamatergic presynaptic neuron and record the response in the postsynaptic neuron with NMDA receptors, what response will you get? Why?
(a) Depolarizing
(b) Hyperpolarizing
(c) No response

Question 23

You identified a new receptor for glutamate. Based on the sequence of the protein you predict that it has seven transmembrane spanning regions. What kind of glutamate receptor do you think this will be most like? Select all that apply.
(a) AMPA
(b) G-protein-coupled receptor
(c) Ionotropic
(d) Metabotropic

Question 24

Fill in the missing words in the following sentence.
Synaptic transmission at the vertebrate neuromuscular junction usually begins with an action potential that triggers the release of the neurotransmitter ____ from the axon terminal. This molecule diffuses across the ________ _____ and binds to the postsynaptic ______. Once this molecule binds, ____ and ____ ions move across the membrane and produce a ____.

Question 25

True/False: Single neurons can only release one type of neurotransmitters. Explain your answer.

Question 26

You take a 'normal' oocyte and apply ACh by iontophoresis to the oocyte and record the resulting current response with voltage clamp
A. What will the resultant current be? Explain.
B. You then inject the oocyte with mRNAs for AChR subunits and apply ACh. What will happen? Explain your answer.

Question 27

How many ACh binding sites are there on each AChR?
(a) 1
(b) 2
(c) 3
(d) 4
(e) 5

Question 28

When a trimeric G protein is activated, it dissociates into two protein complexes. What are these?
(a) Gα and Gβγ
(b) Gαβ and Gγ
(c) Gαγ and Gβ
(d) Gβ and Gαδ

Question 29

To which molecules does PSD95 bind? Choose all that apply.
(a) Neuroligin
(b) GluN2B
(c) Cadherin
(d) Actin

Question 30

You identify a new neuron in the Drosophila brain and find it contains acetylcholine. Based on this identification this neuron is ________. Explain your answer.
(a) Excitatory
(b) Inhibitory
(c) Neither excitatory nor inhibitory
(d) Either excitatory or modulatory

Question 31

In adult neurons, there is a higher concentration of chloride outside the cell than inside the cell. During development intracellular chloride concentrations are much higher such that GABA causes excitation of the postsynaptic neuron. Why could changing the Cl^- concentration result in excitation?
(a) E_Cl is now > action potential threshold.
(b) E_Cl is now < action potential threshold.
(c) There is a smaller Ca²⁺ conductance.
(d) Higher concentrations of Cl^- modulate the GABA_R single channel conductance.

Question 32

Fill in the missing words in the following sentence.
Glutamate is an amino acid. The neurotransmitter, _______, is derived from glutamate by the enzyme _______.

Question 33

Why is the NMDA receptor a good coincidence detector?

Question 34

List properties that differ between ionotropic and metabotropic receptors.

Question 35

Which molecules activate the ionotropic AChR? Choose all that apply.
(a) Nicotine
(b) Muscarine
(c) ACh
(d) Muscimol

Question 36

What is a reversal potential (E_rev)?

Question 37

GABA and glycine activate ionotropic channels that conduct chloride. How does the chloride conductance inhibit excitation? Select all that apply.
(a) It lowers the voltage across the membrane to below action potential threshold.
(b) It blocks activation of the excitatory receptor.
(c) It provides an increased resistance in the membrane, making it more difficult to depolarize the voltage across the membrane.
(d) It provides increased conductance in the membrane, making it more difficult to depolarize the voltage across the membrane.

Question 38

You identify a new neurotransmitter and call it Jerrionin. In order to characterize the actions of this neurotransmitter, you conduct an experiment in which you stimulate the Jerrionin-containing neuron while recording the postsynaptic current using voltage clamp. You get the following results: Figure Q3-27
A. Draw the I-V curve for this response.
B. What is the reversal potential for the Jerrionin receptor? Why did you choose that value?
C. What ion/s is/are most likely to have a high conductance through the Jerrionin channel?

Question 39

How does the G-protein mediated activity terminate?
(a) The GDP replaces GTP.
(b) There is an enzyme that reassembles the trimeric G protein.
(c) The protein contains intrinsic GTPase activity.
(d) Ca²⁺ ions inactivate the protein.

Question 40

Fill in the missing words in the following sentence.
PLC is activated by ______, a Gα variant. Activated PLC cleaves ______ to (1) ______, which in turn activates a serine/threonine kinase called ______, and (2) ______, which in turn binds to its receptor on the membrane of the endoplasmic reticulum (ER) and triggers the release of ______, interacting with an effector protein ______.

Question 41

In Figure Q3-52, a 5-ms depolarizing current pulse was injected into the soma, which produced a single action potential that was recorded in the cell body. Right after that, the distant dendrites of the neuron were activated, which generated a dendritic spike, which propagated to the cell body and resulted in two additional somatic action potentials. What would happen to (A) the first and (B) the second two action potentials if you blocked the dendritic action potentials? Figure Q3-52

Question 42

What is the function of a serine/threonine kinase?
(a) To decrease the action of cAMP
(b) To convert ATP to cAMP
(c) To activate Ca²⁺ channels
(d) To phosphorylate serine or threonine on proteins

Question 43

Otto Loewi won a Noble Prize in 1936 for showing that nerves release chemical transmitters. For one of his experiments he showed that stimulating the vagus nerve caused the heartbeat to slow down. He then collected the 'releasate' from nerve stimulation and put it on another heart, in which the heartbeat slowed as well. The substance that was release was later identified as ACh. What do we know now about the mechanism by which ACh decreases heart rate? Fill in the blanks in the following sentence.
ACh binds to the _____ cholinergic receptor, which activates a specific G protein, ____. This causes the dissociation of the trimeric G protein complex and the _____subunits bind to and activate a class of channels called _______, which OPEN/CLOSE (choose one) and result in ______ions moving INTO/OUT (choose one) of the cell. This DEPOLARIZES/HYPERPOLARIZES (choose one) the muscle cells, slowing the heartbeat.

Question 44

The receptor for which of the following is NOT included in the GPCR superfamily?
(a) Glutamate
(b) Wnt
(c) Photon
(d) Opioids
(e) Androgen

Question 45

Norepinephrine (NE) can bind to the β-adrenergic receptor and speed up heart rate through the cAMP signaling cascade. The cAMP cascade results in the phosphorylation of a voltage-gated Ca²⁺ channel, which increases its open probability. For each situation below state if the Ca²⁺ channel open probability increases, decreases, or does not change.
A. Intracellular addition of cAMP, in the absence of application of NE
B. In the absence of NE application, the inability of GTP to dissociate from Gα
C. In the presence of NE application, the inability of GDP to dissociate from Gα

Question 46

The canonical model for neurotransmitter release is that there is synaptic input to a dendrite which, if large enough depolarizes the voltage across the membrane and generates an action potential at the axon hillock, which travels to the axon terminal and causes the release of neurotransmitter.
Based on the concepts in this chapter, discuss how the properties below alter this model.
A. Active properties of dendrites
B. Inhibition along the dendrite
C. Presynaptic inhibition
D. Summation?

Question 47

Neurotransmitters can result in long-term changes in the physiological state of a neuron. One way this can happen is through activation of transcription factors, like CREB. How can neurotransmitters effect gene expression in neurons? Be as specific as possible.

Question 48

In vertebrate CNS neurons, synapses are on dendritic spines. Most of the postsynaptic receptors are on the spine head, which are attached to the dendrite through a very small spine neck. What is the consequence of this small neck? Select all that apply.
(a) The creation of independent chemical and electrical compartments.
(b) It creates the ability to modulate synaptic inputs independently.
(c) It traps ions in specific locations in the neuron.
(d) It creates the possibility that synaptic connections will be lost over time as they will break off.

Question 49

Synaptic transmission can be potentiated by release of serotonin on the presynaptic terminal. In the experiments shown in Figure Q3-49, investigators used intracellular recording of the neuron and whole-cell patch recording of the potassium channels to understand how serotonin influences the action potential. Figure Q3-49
A. In experiment 1, what happened to the action potential when cAMP and serotonin (5-HT) were added to the extracellular space of the neuron (top trace) and cAMP was injected intracellularly into the neuron (bottom trace)?
B. In experiment 2, what happened to the potassium channel activity when serotonin was added to the outside of the cell and cAMP was added to the inside of the cell?
C. Summarize all the figures. How does serotonin increase the duration of the action potential (include the second messengers in your answer)?

Question 50

One way that nociception (the sensation of pain) is modulated is by presynaptic inhibition of transmitter release from the nociceptive sensory neuron onto its postsynaptic target that takes information to the central nervous system (Figure Q3-48). Endogenous opioids (endorphins) are released onto the presynaptic terminal of the nociceptive sensory neuron. Figure Q3-48
A. If endorphins eventually result in an increased probability of Ca²⁺ channel closure, what will happen to the amount of glutamate release from the sensory neuron? Increase or decrease?
B. What would happen to Ca²⁺ channels if a G protein were activated in the absence of endorphin release?
C. Would endorphin result in synaptic facilitation or depression?

Question 51

There are two main types of integration of signals, what are these and what is the difference between the two?