Learning Outcomes - Week 4 - Synaptic Transmission

Question 1

Understand what is meant by the terms neuromuscular junction, neuroeffector junction, synapse and synaptic transmission.

Define neuromuscular junction

Define neuroeffector junction

Define synapse

Define synaptic transmission

Answer 1

Neuromuscular junction = a synaptic connection between the terminal end of a motor nerve and a muscle (interactions between neurones and muscle)

Neuroeffector junction = the region used for neurones to communicate to other tissues (glands etc.)

Synapse = The region of communication between neurones

Synaptic transmission = The communication that takes place at a structure known as a synapse and the physiological process is referred to as synaptic transmission.

Question 2

Be able to describe the difference between axodendritic, axosomatic and axoaxonic synapses.

Answer 2

axodendritic synapses = When the axon terminal of one neurone forms a functional contact with the dendrite of another neurone (most common types of synaptic interactions in the nervous system)

axosomatic synapses = When the axon terminal of one neurone forms a synapse with the cell body (soma) of another neurones

axoaxonic synapses = fairly unusual interaction where the axon terminal of one neurone forms a functional contact with the axon terminal of another neurone (These types of synapse are involved in modulating (fine-tuning) the process of synaptic transmission)

Question 3

Know the main structural elements of a synapse and the relationship between these.

Answer 3

Parts of the Synapse:

• The presynaptic ending that contains neurotransmitters.
• The synaptic cleft between the two nerve cells.
• The postsynaptic ending that contains receptor sites.

Question 4

T/F: the close apposition of neurones is not sufficient for information to flow between them.

Why?

Answer 4

True

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.

Question 5

Understand the theories of synaptic transmission championed by John Eccles and Henry Dale.

Answer 5

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 6

Be able to describe the structural characteristic of electrical synapses and be able to identify some of the places where they are located:

1. Describe the pre and postsynaptic neurones in relation to one another
2. How are electrical synapses characterised?
3. How are gap junctions formed?
4. What are hemi-channels known as and what are they made up of?

Answer 6

1. The pre and postsynaptic neurones are physically coupled by structures that allow electrical continuity between cells.
2. Electrical synapses are characterised by the very close apposition of the pre- and postsynaptic membranes (resulting in a synaptic cleft of only 3 nm) and the presence of gap-junctions that connect the intracellular space of the two neurones
3. formed by complementary hemi-channels associated with the pre- and post synaptic membrane that provide a low-resistance pathway between the two cells
4. connexons and made up of the protein connexin - each connexon is formed from six connexin molecules which extend 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 7

Understand the difference between rectifying and bidirectional (reciprocal) synapses.

Answer 7

Rectifying synapse - can only pass information in one direction (from the pre- to the postsynaptic neurone) (Note that the action potential in neurone 1 causes a subthreshold depolarisation of neurone 2 but not vice versa)

Bidirectional (or reciprocal) synapses - are able to pass information in either direction (Note that the action potential in neurone 3 causes a subthreshold depolarisation of neurone 4 and vice versa)

Question 8

Be able to describe the structural characteristic of a chemical synapse.

List the steps for this communication to occur:

Answer 8

Communication between the two neurones is enabled by the release of a chemical (known as the neurotransmitter) from the presynaptic neurone.

1. When an action potential arrives in the axon terminal of the the presynaptic neurone the neurotransmitter is released by exocytosis and subsequently diffuses across the synaptic cleft which in this instance is about 30 nm wide.
2. The neurotransmitter then binds to complementary receptors on the postsynaptic membrane
3. The binding of the neurotransmitter to the receptor then initiates changes in the excitability of the postsynaptic neurone
4. (Neurotransmitters are usually synthesised by the presynaptic neurone and stored in synaptic vesicles, that are present in large numbers in axon terminals adjacent to the presynaptic membrane.)

Question 9

Appreciate that there are two major classes of neurotransmitter, that these are stored in different vesicle types and know the names of transmitters belonging to the different families.

Name the neurotransmitters for the classes of the Small Molecule (Classical) Neurotransmitters

Answer 9

Question 10

Understand that some neurotransmitters perform important cellular functions in addition to their roles as neurotransmitters and that many neurones contain more than one neurotransmitter.

Answer 10

Some neurotransmitters in other classes perform important cellular functions in addition to their roles as neurotransmitters.

Question 11

Understand the physiological processes involved in neurotransmitter exocytosis from the presynaptic neurone.

Answer 11

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 12

Be able to describe the mechanisms by which the duration of action of neurotransmitters is limited.

Answer 12

The duration of effects of the neurotransmitter is restricted by a number of mechanisms that act to remove it from the synaptic cleft and therefore limits its actions on postsynaptic receptors:

1. Diffusion

The most common mechanism that limits the duration of a neurotransmitter is simply diffusion of the chemical out of the cleft and into the extracellular space surrounding the synapse. Because the receptors are restricted to the postsynaptic membrane, the neurotransmitter no longer has any effect.

2. Reuptake

Many neurotransmitters are recycled back into the axon terminal, repackaged and used again. This recycling process is enabled by the presence of specific transporters in the membrane of the axon terminal.

3. Enzymatic Degradation

Some neurotransmitters broken down by enzymes located within the synaptic cleft. For example acetylcholine is broken down by acetylcholinesterase into choline and acetate and consequently inactivated.

NOTE: Because both reuptake and enzymatic degradation 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. For example the powerful psychotropic drug cocaine blocks the membrane transporter responsible for the reuptake of the neurotransmitter dopamine. The psychoactive and addictive nature of the drug are believed to be a consequence of the increased dopamine concentration in the synaptic cleft as a result.

Question 13

T/F: Anything that blocks the degradation or reuptake of a neurotransmitter results in an increased in the concentration of the neurotransmitter in the synaptic cleft.

Answer 13

True (because the neurotransmitter is not being removed and uptaken therefore it continues to build at the postsynaptic membrane until degradation or reuptake can occur)

Question 14

Understand what is meant by the term synaptic delay and what contributes to this process.

Answer 14

Post synaptic delay is defined as the time interval between peak of inward current through the presynaptic membrane and commencement of inward current through the postsynaptic membrane.

The synaptic delay is due to the time necessary for transmitter to be released, diffuse across the cleft, and bind with receptors on the postsynaptic membrane. Chemical synaptic transmission is generally unidirectional.

Question 15

Appreciate that it is the receptor for the neurotransmitter that determines whether a synapse is excitatory or inhibitory. Explain and give an example

Answer 15

Whether a synapse is excitatory or inhibitory is determined entirely by the receptor for the neurotransmitter (not the neurotransmitter itself). For example it is possible for the same neurotransmitter to produce depolarisation when it binds to one type of receptor and hyperpolarisation when it binds to another.

Question 16

Be able to describe the fundamental differences between ionotropic and metabotropic neurotransmitter receptors.

Answer 16

One very important feature of ionotropic receptors is that because the potential differences that they elicit are produced directly by the movements of ions, their effect are very rapid in onset (synaptic delay of 0.5 ms) and fairly limited in duration (a few 10’s of ms).

Question 17

What is the ionic-basis of the excitatory postsynaptic potential produced when either glutamate binds to a glutamate receptor or acetylcholine binds to the nicotinic acetylcholine receptor.

Answer 17

A good example of this type of system is the muscarinic acetylcholine receptor that is found on cardiac muscle cells. When acetylcholine binds to this receptor it activates a G protein complex that leads to the formation of a second messenger that acts intracellularly to open a K+ ion channel. Potassium ions leave the cell along their concentration gradient, the membrane hyperpolarises and cardiac muscle is inhibited.

Question 18

Understand the ionic-basis of an inhibitory postsynaptic potential.

Answer 18

A good example of this type of system is the muscarinic acetylcholine receptor that is found on cardiac muscle cells. When acetylcholine binds to this receptor it activates a G protein complex that leads to the formation of a second messenger that acts intracellularly to open a K+ ion channel. Potassium ions leave the cell along their concentration gradient, the membrane hyperpolarises and cardiac muscle is inhibited.

Question 19

What is the relationship between metabotropic receptors, G-proteins, intracellular enzymes and second messengers in relation to synaptic transmission?

Answer 19

1. Neurotransmitter binds to metabotropic receptor
2. G-protein activated and stimulates the enzyme to produce a small second messenger molecule (cAMP, cGMP, Ca^2+, or Nitric oxide)
3. Second messengers freely diffuse through the cytoplasm of the postsynaptic neurone and produce a number of indirect effects (eg: enzyme activation, regulation of gene transcription, ion channels opening, and modification of the sensitivity of ionotropic receptors)

Question 20

1. Know some of the second messengers that are released following metabotropic receptor activation
2. and some of their effects on cellular function.

Answer 20

1. cAMP, cGMP, Ca2+ or nitric oxide
2. indirect effects including enzyme activation, regulation of gene transcription, ion channel opening and modification of the sensitivity of ionotropic receptors

Question 21

Be able to describe the mechanisms by which acetylcholine produces different effects depending on whether it binds to nicotinic or muscarinic acetylcholine receptors.

Answer 21

The molecule acetylcholine activates muscarinic receptors, allowing for a parasympathetic reaction in any organs and tissues where the receptor is expressed. Nicotinic receptors are ionotropic ligand-gated receptors that are also responsive to Ach, but they are mostly in the central nervous system.

Question 22

Understand the different types of summation and be able to explain how these mechanisms underpin the large number of decisions we make every day.

1. How does a neurone add up all the inputs?
2. What is this adding together referred to as and is it in effect is the initial segment that does the arithmetic?

Answer 22

1. The neurone simply adds up all the EPSPs and IPSPs and if the membrane potential reaches threshold then it generates and action potential
2. Summation - yes

Question 23

Appreciate that there are two major classes of neurotransmitter, that these are stored in different vesicle types and know the names of transmitters belonging to the different families.

Name the class and neurotransmitters within for the Peptide Neurotransmitters

Answer 23