Chapter 5 - Synaptic Transmission

Question 1

The many kinds of synapses within the human brain fall into two general classes. Which?

Answer 1

1. Electrical synapses

2. Chemical synapses

Question 2

Shortly: what are the characteristics of electrical synapses?

Answer 2

They permit direct, passive flow of electrical current from one neuron to another.

Question 3

How are neurons with electrical synapses bound together?

Answer 3

Through gap junctions.

Question 4

What are gap junctions?

Answer 4

Gap junctions are the intracellular specialisations that link two neurons together in an electrical synapse. Gap junctions contain precisely aligned, paired channels called connexons.

Question 5

What is a connexon?

Answer 5

Connexons are composed of a special family of ion channel proteins called connexins. Each connexon unit consists of six connexins.

Question 6

What are the advantages of using electrical synapses?

Answer 6

1. The ion current flow can be bidirectional.
2. Transmission is extraordinarily fast.
3. Cells can easily coordinate metabolic activity through the gap junction.

Question 7

Give examples on where you can find an electrical synapse.

Answer 7

• Brainstem neurons that generate rhythmic electrical activity underlying breathing are synchronised by electrical synapses.

Question 8

Chemical synaptic transmission: An action potential invades the presynaptic terminal. What happens thus?

Answer 8

Depolarisation of presynaptic terminal causes opening of voltage-gated Ca2+ channels.

Question 9

Chemical synaptic transmission: Depolarisation of presynaptic terminal causes opening of voltage-gated Ca2+ channels. What happens thus?

Answer 9

Influx of Ca2+ through the voltage-gated Ca2+ channels. This is because the concentration of Ca2+ is much higher on the outside of the membrane, and the membrane is more negative on the inside.

Question 10

Chemical synaptic transmission: Influx of Ca2+ through the voltage-gated Ca2+ channels. What happens thus?

Answer 10

Ca2+ causes vesicles to fuse with presynaptic membrane.

Question 11

Chemical synaptic transmission: Ca2+ causes vesicles to fuse with presynaptic membrane. What happens thus?

Answer 11

Transmitter is released into synaptic cleft via exocytosis.

Question 12

Chemical synaptic transmission: Transmitter is released into synaptic cleft via exocytosis. What happens thus?

Answer 12

Transmitter binds to receptor molecules in postsynaptic membrane.

Question 13

Chemical synaptic transmission: Transmitter binds to receptor molecules in postsynaptic membrane. What happens thus?

Answer 13

Opening or closing of postsynaptic channels.

Question 14

Chemical synaptic transmission: Opening or closing of postsynaptic channels. What happens thus?

Answer 14

Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell.

Question 15

How is transmitter removed from the cell?

Answer 15

• Glial uptake
• Enzymatic degradation
• Diffusion away from the synapse.
• Reuptake into nerve terminals.

Question 16

Vesicles are made out of?

Answer 16

Plasma membrane and other molecules.

Question 17

The notion that electrical information can be transferred from one neuron to the next by means of chemical singling was the subject of intense debate throughout the first half of the twentieth century. One famous experiment was conducted in 1926…

Answer 17

In 1926, the German physiologist Otto Loewi performed a key experiment that suppored this idea. Acting on an idea that allegedly came to him in the middle of the night, Loewi proved that electrical stimulation of the vagus nerve slows the heartbeat by releasing a chemical signal. He isolated and perfused the hearts of two frogs, monitoring the rates at which they were beating. When the vagus nerve innervating the first heart was stimulated, the beat of this heart slowed. Remarkably, even through the vagus nerve of the second heart had not been stimulated, its beat also slowed when exposed to the perfusate from the first heart. This result showed that the vagus nerve regulates the heart by releasing a chemical that accumulates in the perfusate.

Question 18

Otto Loewi proved that electrical stimulation of the vagus nerve slows the heartbeat by releasing a chemical signal. He called that chemical “vagus substance”. This agent was later shown to be what we now call …

Answer 18

acetylcholine (ACh).

Question 19

Two broad categories of neurotransmitters exist. They are…

Answer 19

1. Small-molecule neurotransmitters

2. Neuropeptides

Question 20

The synthesis of small-molecule neurotransmitters occurs where?

Answer 20

It occurs locally within presynaptic terminals.

Question 21

The synthesis of small-molecules neurotransmitters is dependent / independent on the functions of the cell soma.

Answer 21

It is dependent. Even though the synthesis happens in the presynaptic terminal, the components that allow this to happen, like the enzymes needed, are all produced in the neuronal cell body and are then transported ti the nerve terminals.

Question 22

Transport of enzymes necessary for the production of small-molecule neurotransmitters is done how?

Answer 22

Via slow axonal transport.

Question 23

The vesicles of small-molecule neurotransmitters are of which type?

Answer 23

Most small-molecules neurotransmitters are packaged in vesicles 40-60nm in diameter, the centres of which appear clear in electron micrographs; accordingly, these vesicles are referred to as small clear-core vesicles.

Question 24

The synthesis of neuropeptides occurs where?

Answer 24

Neuropeptides are synthesised in the cell body of a neuron, meaning that the peptide is produced a long distance away form its site of secretion.

Question 25

The synthesis of neuropeptides is dependent / independent on the functions of the cell soma.

Answer 25

Dependent. They’re produced in the soma.

Question 26

Transport of neuropeptides is done how?

Answer 26

Peptide-filled vesicles are transported along an axon and down to the synaptic terminal via fast axonal transport. This process carries vesicles along cytoskeletal elements called microtubules.

Question 27

What are microtubules and how do they work?

Answer 27

Microtubules are long, cylindrical filaments, 25nm in diameter, present thought neurons and other cells. Peptide-containing vesicles move along these microtubule “tracks” by ATP-requiring “motor” proteins such as kinesin.

Question 28

The vesicles of neuropeptides are of which type?

Answer 28

Neuropeptides are packaged into synaptic vesicles that range from 90-250 nm in diameter. Because the center of these vesicles appear electron-dense in electron micrographs, they are referred to as large dense-core vesicles.

Question 29

Is there a difference between the two categories of neurotransmitters in terms of their removal from the synaptic cleft?

Answer 29

Specific transported proteins remove most small-molecule neurotransmitters (or their metabolites) form the synaptic cleft, ultimately delivering them back to the presynaptic terminal for reuse.

Question 30

What is meant by Quantal release of neurotransmitters?

Answer 30

Research by Bernhard Katz and his collaborators in the 1950s and 1960s revealed that depolarisations in the muscle cells occurred both after an action potential has reached the presynaptic terminal, and as smaller spontaneous depolarisations. This lead to an hypothesis that the end plate potentials in the muscles could be represented as the simultaneous release of many miniature end plate potential-units. Release of neurotransmitter is quantal because it involves the simultaneous release of many equal units.

Question 31

What keeps the synaptic vesicles together as they are stored?

Answer 31

Several lines of evidence indicate that the protein Synapsin, which reversibly binds to synaptic vesicles, may keep these vesicles tethered within the reserve pool by crosslink vesicles to each other and to actin filaments in the cytoskeleton.

Question 32

What causes the stored and synapsin-linked vesicles to move away from the storage area?

Answer 32

Mobilisation of these reserve pool vesicles is caused by phosphorylation of synapsin by protein kinases. This allows synapsin to dissociate form the vesicles.

Question 33

What happens to the vesicles that have been released from the reserve pool by phosphorylation?

Answer 33

They make their way to the plasma membrane and are attached to this membrane by poorly understood docking reactions.

Question 34

Which docking reactions were the saddest in high school?

Answer 34

The poorly understood docking reactions.

Question 35

What happens after the vesicles have been attached to the plasma membrane of the synaptic bouton?

Answer 35

A series of priming reactions prepare the vesicular and plasma membranes for fusion. The involve a large number of proteins. You don’t need to remember all of these, but they are: NSF, SNAPs, SNAREs (synaptobrevin, syntax and SNAP-25).

Question 36

A protein involved in priming is synaptotagmin. What is special about it?

Answer 36

Synaptotagmin is a protein found in the membrane of synaptic vesicles. It binds Ca2+ at concentrations similar to those required to trigger vesicle fusion with the presynaptic terminal. Disruption of synaptotagmin in the presynaptic terminals of mice, fruit flies, squid, and other experimental animals impairs Ca2+-dependent neurotransmitter release. Deletion of only one of the 19 synatotagmin genes in mice is a lethal mutation.

Question 37

What is the most important protein involved in endocytotic budding of vesicles from the plasma membrane?

Answer 37

Clathrin.

Question 38

There are two broad families of receptor proteins. Which, and how do they differ?

Answer 38

1. Ionotropic receptors
2. metabotropic receptors

They differ in their mechanism of transducing transmitter binding into postsynaptic responses.

Question 39

Ligand-gated ion channels is another term for …

Answer 39

Ionotropic receptors.

Question 40

G-protein-coupled receptors is another term for …

Answer 40

Metabotropic receptors.

Question 41

Apart from their transducing mechanism, what sets the Ionotropic receptors apart from the Metabotropic receptors?

Answer 41

The conductance speed. The ionotropic receptors generate postsynaptic potentials PSPs faster.

Question 42

Why are the metabotropic receptors slower?

Answer 42

The comparative slowness of metabotropic receptor actions reflects the fact that multiple proteins need to bind to each other sequentially in order to produce the final physiological response.

Question 43

What is meant by EPSP?

Answer 43

Excitatory postsynaptic potential. It is a change in the postsynaptic potential that increases the likelihood of a postsynaptic action potential occurring.

Question 44

What is meant by IPSP?

Answer 44

Inhibitory postsynaptic potential. It is a change in the postsynaptic potential that decreases the likelihood of a postsynaptic action potential occurring.

Question 45

What is meant by summation of synaptic potentials?

Answer 45

Neurons in the central nervous system are typically innervated bu thousands of synapses, and the PSPs produced by each active synapse can sum together - in space and time - to determine the behaviour of the postsynaptic neuron. Summation thus allows sub threshold EPSPs to influence action potential production.