Lecture 7 - Synaptic Transmission I

Question 1

True or False?:

If you’re trying to coordinate motor output (in the heart for example), you often gap junction the cells together so that they fire at almost the exact same time.

Answer 1

True

Question 2

True or False?:

Gap junctions can pass current, but not small signaling molecules, such as cAMP and ATP.

Answer 2

False

Gap junctions can pass current, as well as small signaling molecules, such as cAMP and ATP.

Question 3

Which protein complex is resposible for docking, priming, and fusion? What key structural characteristics does it possess and what is it composed of?

Answer 3

Docking, priming, and fusion are dependent on the SNARE protein complex. The SNARE complex forms a very tight helical structure that is very resistant to denaturing. It is made up of SNAP-25, synaptobrevin, and syntaxin.

Question 4

How are postsynaptic neurons depolarized through gap junctions?

Answer 4

If you depolarize one cell, the ions in it can propagate through gap junctions to a neighbouring cell and depolarize that cell, resulting in a direct depolarization of the neighbouring cell.

Question 5

True or False?:

Connexons are built out of rosettes of 4 connexin proteins that traverse the presynaptic and postsynaptic membranes.

Answer 5

False

Connexons are built out of rosettes of 6 connexin proteins making a hemichannel that binds with a hemichannel from a neighbouring cell to make a full gap junction channel.

Question 6

True or False?:

Muscles have their own version of an action potential driven by potassium that drives the contration of the muscle fibres.

Answer 6

False

Muscles have their own version of an action potential driven by calcium that drives the contration of the muscle fibres..

Question 7

True or False?:

In exocytosis during neurotransmitter release, synaptotagmin is the trigger but the SNARE proteins are what drive the fusion itself.

Answer 7

True

Question 8

True or False?:

The neuromuscular junction is so large because only one neuron innervates a given muscle.

Answer 8

True

Question 9

True or False?:

Electrical synapses are typical cell body to cell body contacts or dendrite to dendrite contacts. They are not necessarily an axon projecting far away and making gap junction connections.

Answer 9

True

Question 10

What happens if you inject a calcium buffer into a presynaptic neuron (of a chemical synapse)?

Answer 10

There will still be a presynaptic membrane potential, but the calcium will be binded and unable to signal for the release of neurotransmitter resulting in no postsynaptic response.

Question 11

What is pictured in the following EM images?

Answer 11

Gap Junctions

Question 12

Which type of synapse is also called a gap junction?

Answer 12

Electrical

Question 13

When looking at a chemical synapse EM image, what would you look for to identify which neuron is pre-synaptic?

Answer 13

Vesicles

Question 14

What does it mean to say that connexins are homophilic?

Answer 14

Connexins are typically homophilic in the sense that if you have connexin 43, it will typically bind with a connexin 43 on the other membrane.

Question 15

True or False?:

In traditional vesicle recycling, clathrin starts to form a vesicle off of the plasma membrane and dynamin cuts it off.

Answer 15

True

Question 16

What are the three defining traits of a neurotransmitter?

Answer 16

• It must be present within the pre-synaptic neuron.
• It must be released in a depolarization and calcium dependent fashion.
• It must have specific receptors on the post-synaptic neurons.

Question 17

Which proteins are responsible for setting up the SNARE proteins but not actually involved with fusion themselves? What happens if they are deleted?

Answer 17

Munc18 and Munc13

Fusion will not occur if they are deleted.

Question 18

True or False?:

At chemical synapses, a chemical signal is converted to an electrical signal which is then converted back to a chemical signal.

Answer 18

False

At chemical synapses, an electrical signal is converted to a chemical signal which is then converted back to an electrical signal.

Question 19

What happens if you inject a small amount of calcium into a presynaptic neuron (of a chemical synapse)?

Answer 19

Neurotransmitter will be released which will trigger a postsynaptic response.

Question 20

How did Loewi prove his hypothesis?

Answer 20

Loewi set up two hearts in solution. One was attached to the vagus nerve and one was not. When the vagus nerve was simulated, the heart rate of its connected heart decreased. Shortly after, the heart rate of the nonconnected heart also decreased. This proved that a chemical substance entered the solution to trigger this response in the second heart.

Question 21

How does the cell’s ability to regulate calcium affect the small clear vesicles’ and large dense-core vesicles’ abilities to react to action potentials?

Answer 21

The cell is very good at regulating intracellular calcium (through buffering and binding proteins) and exists in “micro-domains”, or very small regions around the calcium channels they entered in. Small clear vesicles dock close enough to the calcium channels that they exists in these “micro-domains” and will be triggered by any action potential. Large dense-core vesicles are positioned further away from the channels than the small clear vesicles and do not experience the effect of a single action potential. To trigger the fusion of dense-core vesicles, there must be multiple action potentials in a row resulting in enough calcium entering the cell to reach them.

Question 22

What are gap junctions useful for? What are gap junctions not useful for? Why?

Answer 22

Gap junctions are useful for directly depolarizing a neighbouring cell but are not a useful way to propagate a signal over a long distance through multiple cells because the signal decays through intercellular transmission as not all of the current (ions) pass through the gap junctions (resistors) fast enough to cause an equally strong depolarization in the postsynaptic cell.

Question 23

What is unique about synaptic vesicles and the priming process?

Answer 23

Normal vesicles that are carrying a membrane protein through the cytosol to the plasma membrane meet with the membrane and fuse with it in one process. Synaptic vesicles have implemented a “break” on the process. The process starts but does not complete itself until signaled by the influx of calcium (detected by synaptotagmin) during an action potential.

Question 24

Which are small clear or large dense-core vesicles more sensitive to calcium? Why?

Answer 24

Large dense-core vesicles are more sensitive to calcium because they are located further away from the channels and must be able to sense the small amount of calcium they will encounter.

Question 25

What are the key events in vesicle cycling?

Answer 25

1. A vesicle full of neurotransmitter buds from an endosome.
2. The vesicles dock and prime to the interior of the presynaptic membrane until the influx of calcium (from opening of voltage-gated channels caused by action potential) cause them to fuse with the presynaptic membrane.
3. Transmitter is released into the synaptic cleft via exocytosis.
4. The vesicular membrane buds from the plasma membrane and goes back to an endosome so that the membrane can be reused.

Question 26

What are the two basic types of connections (synapses) between neurons?

Answer 26

Electrical and Chemical

Question 27

What did Loewi’s hypothesis state?

Answer 27

Nerve simulation releases a chemical substance that either slows or speeds up the heart rate. Each nerve releases a separate chemical with different effects.

Question 28

What is a spontaneous MEPP?

Answer 28

A spontaneous miniature end-plate potential is a small depolarizing event in the postsynaptic membrane at the neuromusuclar junction caused by a “leak” in neurotransmitter from the presyanptic neuron.

Question 29

Which protein interacts with SNARE proteins to drive fusion? Why is it important?

Answer 29

Synaptotagmin interacts with the SNARE proteins on the vesicle to drive fusion. It is important because it is calcium-sensitive.

Question 30

What do gap junctions function as (electrically)? How does this affect the membrane potential in the postsynaptic cell?

Answer 30

Gap junctions act as resistors, as current (ions) have to pass through a small pore. Not all of the current makes it through the resistor, and it does not pass through instantaneously. As such, the membrane potential peak in the postsynaptic cell will have a brief synaptic delay, a slightly shorter amplitude, and be more stretched out in time.

Question 31

What are the four main steps of exocytosis (docking, priming, fusion) during neurotransmitter release (in detail)?

Answer 31

1. SNARE complexes form from synaptobrevin on the vesicle and syntaxin and SNAP-25 on the plasma membrane.
2. Synaptotagmin binds to the newly formed SNARE complex.
3. Entering calcium binds to synaptotagmin, leading to curavture of the plasma membrane, which brings it and the vesicular membrane together.
4. The membranes fuse, leading to the exocytotic release of neurotransmitter.

Question 32

If you want to measure postsynaptic response in a muscle cell, what should you measure?

Answer 32

End Plate Potential (EPP)

Question 33

What are two ways in which membrane can be recycled during vesicle cycling (quick and long way)? What is the debate surrounding one of these methods?

Answer 33

A vesicle can fuse very briefly before pinching off and returning to the endosome (kiss-and-run) or completely fuse into the membrane before returning to the endosome with the assistance of clathrin. There is debate as to whether kiss-and-run really happens because we are unsure whether a brief fusion will allow for all the neurotransmitter to be released. If only some of the neurotransmitter is released, it would act as a site of control and would interfer with the quantum nature of a chemical synapses.

Question 34

True or False?:

Synaptobrevin and synaptotagmin are found on the plasma membrane while syntaxin and SNAP-25 are found on the vesicle.

Answer 34

False

Synaptobrevin and synaptotagmin are found on the vesicle while syntaxin and SNAP-25 are found on the plasma membrane.

Question 35

What makes chemical signals better than electrical signals?

Answer 35

Electrical signals decay after every electrical synapse, but a chemical synapse allows you to recreate the signal every time. This means it will be able to travel further/through more cells.

Question 36

Which ion is responsible for neurotransmitter release? How was this proven?

Answer 36

Calcium is responsible for neurotransmitter release.

While blocking sodium and potassium, a voltage clamp was performed on the squid giant synpse. When the presynaptic cell was depolarized, a large presynaptic calcium current was seen that led to a postsynaptic membrane depolarization. When calcium was also blocked, this depolarization was not seen.

Question 37

What gives rise to the quantal nature of neurotransmitter release?

Answer 37

Synaptic Vesicles

Question 38

True or False?:

Connexon pores are relatively big and are not selective like many other membrane proteins are.

Answer 38

True

Question 39

Where are most presynaptic vesicles found?

Answer 39

They are found in the reserve pool.

Question 40

What did Loewi name the substance being relesed from the vagus nerve?

Answer 40

Vagusstoff

Question 41

Which synapse is folded in on itself to increase the surface area for signalling?

Answer 41

Neuromuscular Junction

Question 42

How many transmembrane domains are found in connexin proteins?

Answer 42

4

Question 43

True or False?:

Dense core vesicles are made and filled in the cell body and transported down the axon to the terminal while the small clear are made and filled in the terminal themselves.

Answer 43

True

Question 44

What did Sherrington discover that led him to identify and name the synapse?

Answer 44

Sherrington discovered that basket cells have discrete axonal terminals contacting neighbouring neurons.

Question 45

Which technique allows for imaging of an entire membrane surface (as opposed to a cross-sectional view)?

Answer 45

Freeze Fracturing

Question 46

What do gap junction channel proteins (connexons) create (in terms of presynaptic neuron to postsynaptic neuron)?

Answer 46

They create an open pore between the inside of a presynaptic neuron and the inside of a postsynaptic neuron allowing you to bypass the plasma membrane to send signals from one cell to another.

Question 47

True or False?:

Gap junctions link cells during development before they form chemical synapses with eachother.

Answer 47

True

Question 48

What data proved that neurotransmitter release at the neuromuscular junction is quantized?

Answer 48

When comparing the EPP amplitude to the number of EPPs at that amplitude, there are various peaks seen at regular intervals separated by distinct gaps. These peaks imply that neurotransmitter is released quantally and that multiple quantums of neurotransmitter can act postsynaptically at the same time. As further proof, in the distribution below, one EPP quantum (miniature EPP (MEPP)) has the same amplitude as the spontaneous MEPPs measured in muscle fibres.

Question 49

True or False?:

Voltage gated calcium channels are located directly opposite of transmitter receptors in the synaptic cleft.

Answer 49

True

Question 50

True or False?:

Small clear vesicles are filled with slow neuro-peptides like dynorphin and enkephalin while large dense-cour vesicles are filled with fast neurotransmitter like glutamate, GABA, and ATP.

Answer 50

False

Small clear vesicles are filled with fast neurotransmitter like glutamate, GABA, and ATP while large dense-cour vesicles are filled with slow neuro-peptides like dynorphin and enkephalin.

Question 51

True or False?:

Gap junctions coordinate the local activity of oligodendrocytes. They use gap junctions to propagate small signals using signalling molecules to trigger calcium waves that can propagate through entire networks of oligodendrocytes.

Answer 51

False

Gap junctions coordinate the local activity of astrocytes. They use gap junctions to propagate small signals using signalling molecules to trigger calcium waves that can propagate through entire networks of astrocytes.