Week 4 - Synaptic Transmission

Question 1

Where does the communication between neurones take place? what is the physiological process called?

Answer 1

at a structure known as a synapse and the physiological process is referred to as synaptic transmission

Question 2

Taipoxin is the most lethal __________ found in any snake

Answer 2

Neurotoxin

Question 3

What are the most common types of synaptic interactions within the nervous system?

Answer 3

Axodendritic synapses

Question 4

What type of synapse is this?

Answer 4

Axodendritic synapse

Question 5

What types of synapse is this?

Answer 5

Axosomatic synapse

Question 6

What type of synapse is this?

Answer 6

axoaxonic synapse

Question 7

Name the neurone the signal comes from, the neurone the signal goes to, and the space in between, and name the membrane of each of the neurones

Answer 7

The presynaptic neurone

The postsynaptic neurone

The synaptic cleft

Question 8

T/F: The close apposition of the two neurones is not sufficient for information to flow between them. It has been shown that if there is no synapse present an action potential in one neurone only produces a very very small depolarisation (around 1 microvolt) in an adjacent neurone. Clearly this is insufficient to open voltage-gated Na+ channels in the postsynaptic cell and trigger an action potential.

Answer 8

True

Question 9

If the close apposition of two neurones is not enough to enable communication how then is an action potential in one neurone relayed to another at a synapse? Who were the two men who posited the theories on this fix?

Answer 9

John Eccles - believed that a low resistance pathway existed between the presynaptic and postsynaptic neurones and that synaptic transmission was enabled by electrical coupling.

Henry Dale - argued that the action potential in the presynaptic neurones released a chemical that bridged the synaptic cleft and was responsible for the action potential in the postsynaptic neurone.

Both exist

Question 10

Label these

Answer 10

Question 11

What is this describing?

Answer 11

The complementary hemi-channels associated with the pre- and post synaptic membrane that provide a low-resistance pathway between the two cells - These hemi-channels are known as connexons which are made up of the protein connexin. Each connexon is formed from six connexin molecules which extend a uniform distance outside the cells. Alignment of connexons from each cell across the gap results in the formation of aqueous pores roughly 2 nm in diameter between the two cells that functionally define the gap junction.

Question 12

T/F: As a consequence of these gap-junctions an action potential in the presynaptic neurones is able to traverse the synaptic cleft and depolarise the postsynaptic neurone

Answer 12

True

Question 13

What is this?

Answer 13

Rectifying synapse

Question 14

Where were electrical synapses first described? What were they involved in?

How is it useful?

Answer 14

The crayfish

Fairly simple escape reflex helping the cray to avoid predators

Useful because no significant delay between pre- and postsynaptic neurone, therefore, communication is very rapid

Question 15

What are these?

Answer 15

Synaptic vesicles within the axon terminal of a neurone - The most prolific of these are of small diameter and have a clear (translucent) core whilst the others are large diameter dense-cored vesicles

Question 16

T/F: Evidence suggests that these two types of vesicles contain different classes of neurotransmitter:

Answer 16

True

Question 17

Who got the Nobel Prize for the discovery of neurotransmitters for medicine in which year?

Answer 17

Otto Loewi and Henry Dale in 1936

Question 18

Small molecule neurotransmitters are packaged in _____ _______ _____ ________ and include four major classes of chemical.

Answer 18

small diameter clear vesicles

Question 19

T/F: acetylcholine is the only neurotransmitter in its class and that some neurotransmitters in other classes perform important cellular functions in addition to their roles as neurotransmitters.

Answer 19

True

Question 20

T/F: more than one type of synaptic vesicle type and consequently neurotransmitter coexistence. Although some neurones do contain only one small molecule neurotransmitter, many also contain one (or more) peptide neurotransmitters in addition.

Answer 20

True

Question 21

Describe the chain of effects for neurone communication through chemical transmission:

Answer 21

1. Neurotransmitter release at a synapse is initiated by the arrival of an action potential in the axon terminal
2. As the action potential spreads through the axon terminal it triggers the opening of a population of voltage-gated Ca2+ channels
3. With an extracellular Ca2+ of 1.8 mM and an intracellular concentration of 100 nM there is clearly a concentration gradient that encourages the flow of Ca2+ into the axon terminal
4. So as soon as these channels open, Ca2+ rushes into the axon terminal down its concentration gradient
5. The consequent increase in intracellular Ca2+ concentration triggers the migration of synaptic vesicles and their subsequent fusion with the presynaptic membrane
6. The vesicle membrane then breaks down and the neurotransmitters is exocytosed into the synaptic cleft
7. The neurotransmitter then diffuses across the synaptic cleft and binds to its receptors on the postsynaptic membrane

Question 22

Because both _________ and __________ __________ reduce the effective concentration of the neurotransmitter in the synaptic cleft, manipulation of these systems can have quite dramatic effects on the efficacy of synaptic transmission.

Answer 22

reuptake

enzymatic degradation

Question 23

Although the individual molecular events involved in chemical synaptic transmission occur fairly quickly, collectively these constitutes a small but significant delay between the action potential arriving in the axon terminal and the effects of the neurotransmitter be manifest in the postsynaptic neurone. The sum of the times that it takes for Ca2+ channel opening, Ca2+ diffusion, synaptic vesicle migration, exocytosis, diffusion and binding of the neurotransmitter and the changes produced in the postsynaptic neurone contribute to a synaptic delay of approximately…?

Answer 23

0.5 ms

Question 24

Which is faster - Synaptic transmission in chemical synapses or in electrical synapses.

Answer 24

Electrical synapses (because the exachange of neurotransmitters doesn’t need to take place which adds to roughly 0.5ms delay)

Question 25

Is chemical transmission delay an issue in reflex arcs with mono- or disynaptic pathways?

What is it an issue in?

Answer 25

No.

Pathways that involve many synaptic interactions (e.g: Memory pathways - which do require a little more processing time)

Question 26

What kind of receptor is this?

Answer 26

Ionotropic receptor

Question 27

What are ionotropic receptors?

What happens when a neuron binds to an ionotropic receptor?

What is the net effect of opening of these ions channels?

Answer 27

examples of the ligand-gated ion channels that we heard about in the excitable tissues lesson earlier in semester. When a neurotransmitter binds to an ionotropic receptor (see opposite) the channel opens and allows ions to diffuse across the membrane according to their concentration gradient.

The net effect of opening of these ion channels is either depolarisation of the postsynaptic neurone (if it is an excitatory synapse) or hyperpolarisation (if it is an inhibitory synapse).

Question 28

What happens at an excitatory synapse?

Answer 28

an action potential in the presynaptic neurone produces a transient depolarisation of the postsynaptic neurone after the 0.5 ms synaptic delay. Although this is a type of depolarising graded potential, when we are talking about synapses we refer to it more specifically as an excitatory postsynaptic potential (EPSP).

Question 29

What does this diagram show?

Answer 29

The diagram opposite shows the membrane potentials of a presynaptic and postsynaptic neurone that are connected by an excitatory chemical synapse. An action potential in the presynaptic neurone is followed by an EPSP in the postsynaptic neurone.

Question 30

How is the EPSP produced?

What does this do?

What happens in the instance of the glutamate and nicotinic acetylocholine receptor?

Answer 30

The EPSP is produced by binding of the neurotransmitter to ionotropic receptors on the postsynaptic membrane

This opens the ion channel

In the specific instances of the glutamate and nicotinic acetylcholine receptor this appears to be a non-selective cation channel that permits the simultaneous movement of both K+ and Na+ across the membrane.

Question 31

How is the EPSP produced?

What does this do?

What happens in the instance of the glutamate and nicotinic acetylocholine receptor?

What happens as a consequence?

What is the movement of Na+ into the cell helped by?

What is the net effect?

Because the EPSP takes the membrane potential closer to threshold, we think about it ___________________ of the postsynaptic neurone.

Answer 31

The EPSP is produced by binding of the neurotransmitter to ionotropic receptors on the postsynaptic membrane

This opens the ion channel

In the specific instances of the glutamate and nicotinic acetylcholine receptor this appears to be a non-selective cation channel that permits the simultaneous movement of both K+ and Na+ across the membrane.

Na+moves into the cell whilst K+ moves out of the cell down their respective concentration gradients.

the movement of Na+ into the cell is helped by the electrical gradient (it is attracted by the negative resting membrane potential) so more Na+ ions enter the cell than K+ leave the cell

net effect is an influx of positive charge that is directly responsible for the transient depolarisation of the EPSP.

increasing the excitability

Question 32

At an inhibitory synapse an action potential in the presynaptic neurone produces a _________ ____________ of the postsynaptic neurone. This hyperpolarising graded potential is referred to more specifically as an ____________________ when we are talking about synaptic transmission.

Answer 32

transient hyperpolarisation

inhibitory postsynaptic potential (IPSP)

Question 33

What does the diagram opposite show?

Answer 33

The diagram opposite shows the membrane potential of a presynaptic and postsynaptic neurone that are connected by an inhibitory chemical synapse. An action potential in the presynaptic neurone is followed by an IPSP in the postsynaptic neurone.

Question 34

Describe the process of an IPSP being produced and what the result is:

Answer 34

1. The IPSP is produced by binding of the neurotransmitter to ionotropic receptors on the postsynaptic membrane
2. This opens the ion channel
3. The IPSP is most commonly caused by neurotransmitters (such as glycine and gamma-aminobutyric acid), that open ligand-gated Cl- channels
4. The concentration gradient for Cl- favours the movement on this anion into the cell
5. So as a consequence of these channels opening there is a net influx of negative charge that results in hyperpolarisation of the postsynaptic neurone.
6. Because the IPSP takes the membrane potential away from threshold we think about it decreasing the excitability of the postsynaptic neurone or inhibiting it.

Question 35

Depending on the type of channel to which they are connected, ionotropic receptors can either ________ or ________ postsynaptic neurones

Answer 35

excite or inhibit

Question 36

T/F: Thus neurotransmitters are the only source of the excitatory and inhibitory stimuli

Answer 36

False - they are only one source

Question 37

What is the synaptic delay due to ionotropic receptors and what is it the result of?

Answer 37

0.5ms, result of the potential difference they elicit being produced directly by the movement of ions

Question 38

Activation of this second class of neurotransmitter receptor elicits a __________ of molecular events within the postsynaptic neurone that in turn mediate the effects of the neurotransmitter

Answer 38

cascade

Question 39

Metabotropic receptors:

Binding of the neurotransmitter to the receptor activates the ________ which in turn stimulates the enzyme to produce a _______ ________ ________ _________ such as ____________________

Answer 39

G-protein

small molecule second messenger

cAMP, cGMP, Ca2+ or nitric oxide

Question 40

Why are the second messengers in metabotropic receptor chain important?

Answer 40

These second messengers are able to freely diffuse through the cytoplasm of the postsynaptic neurone and in turn produce a number of indirect effects including enzyme activation, regulation of gene transcription, ion channel opening and modification of the sensitivity of ionotropic receptors

Question 41

How fast is the metabotropic receptor mediated synaptic transmission?

Answer 41

Fairly slow - 100ms - therefore not involved in neuronal circuits that require rapid communication - but can result in changes to the metabolism of neurones

Question 42

Which type of receptor and neurotransmitter have a more persistent effect?

Answer 42

Metabotropic receptors as their neurotransmitter can result in changes to the metabolism of neurones

Question 43

T/F: single neurones in the human spinal cord have been shown to receive over 10,000 synaptic inputs

And are some of these excitatory and some inhibitory?

Answer 43

True

Yes

Question 44

Because graded potentials only affect regions of the cell close to where they originate, synapses that are close to the initial segment have a much bigger impact on the neurone than synapses further away. For this reason excitatory or inhibitory effects on the ______ or ___________ _________ affect the neurone to a much greater extent that those out on the ________ dendrites.

Answer 44

soma

proximal dendrites

distal

Question 45

Describe this diagram

Answer 45

The diagram on the right shows neurone 1 and neurone 2 forming an excitatory synapse with neurone 3. The membrane potential of each neurone is displayed below them

The diagram on the right shows neurone 1 and neurone 2 forming an excitatory synapse with neurone 3. The membrane potential of each neurone is displayed below them

However when you stimulate neurone 1 and 2 together you see that the two EPSPs add together, the membrane of neurone 3 reaches threshold and you get an action potential.

Because this type of interaction is from spatially distinct inputs it is referred to as spatial summation.

Question 46

Describe the diagram

Answer 46

In the example opposite two neurones are linked by an excitatory chemical synapse. The membrane potential of the two neurones is displayed below them .

If we stimulate neurone 1 once we get an EPSP in neurone 2 that is below threshold so no action potential occurs.

However if we apply two stimuli to neurone 1 in short succession then see that the EPSP caused by the second action potential arrives before the first one has completely decayed. As a result these two EPSPs add together and consequently neurone 2 reaches threshold and we get an action potential.

Because this type of summation is a consequence of timing of the inputs it is known as temporal summation.

Question 47

Describe the diagram

Answer 47

In the diagram opposite we have a neuronal circuit in which neurone 1 and neurone 2 synapse with neurone 3 and their respective membrane potentials are shown below .

If you stimulate neurone 1 alone you will see that in this instance the EPSP is big enough to reach threshold so we get an action potential in neurone 3.

If you stimulate neurone 2 alone 0 you will see that it must form an inhibitory synapse with neurone 3 because it produces an IPSP.

However when you stimulate neurone 1 and 2 together the IPSP negates the effect of the EPSP and so no action potential is elicited in neurone 3.

This is an example of excitatory and inhibitory synapses can interact.

Question 48

What does the outcome of the constant summation that is occurring in our bodies every second of every day determine?

Answer 48

The outcome of this summation determines what you choose for breakfast, when you will cross the road and the hundred of thousands of other decisions that you make every day.