Lecture 10 - synaptic transmission

Question 1

How does synaptic transmission begin?

Answer 1

In the active zone of the presynaptic terminal, synaptic vesicles cluster against the plasma membrane.

Question 2

How does the binding occur?

Answer 2

A neurotransmitter acts selectively on a specific target in order to elicit some sort of postsynaptic response

Question 3

What determines whether the NT will bind?

Answer 3

The shape and the charge of the NT compliments the binding site on the receptor

Question 4

Which direction do chemical synapses convey information?

Answer 4

Information flow at a chemical synapse is unidirectional and involves the conversion of an action potential into a chemical message

Question 5

Which two classes can NTs be split into?

Answer 5

1 - involves the activation of an ion channel

2 - involves the activation of G-proteins

Question 6

How can signal transduction affect neurons?

Answer 6

It can alter neuronal function on vastly different time scales ranging from very rapid (millisecond) changes in membrane potential to changes over seconds produced by intracellular second messengers and protein kinases.

Question 7

What happens when a NT binds to a receptor?

Answer 7

It affects the functioning of that receptor.

In some circumstances, binding to a receptor can open a pore that allows ions to flow in and out of a neuron.

However, neurotransmitter binding to a receptor can initiate a cascade of signalling events inside of a neuron.

Question 8

What happens when neuron binds to ionotropic receptors?

Answer 8

Neurotransmitter binds to the ionotropic receptors, thus causing a change in shape resulting in channel to open and ions to travel through

Question 9

What do most ionotropic receptors consist of?

Answer 9

Most ionotropic receptors consist of 4 or 5 transmembrane spanning subunits that couple together to form the ion channel complex.

Question 10

What does each subunit consist of?

Answer 10

Each subunit that forms the ionotropic nicotinic acetylcholine receptor consists of 4 alpha helices that span the membrane.

Question 11

How is nicotinic acetylcholine receptor important?

Answer 11

Nicotinic AChRs are involved in a wide range of physiological processes, including muscle contractions and cognition.

Question 12

How does acetylcholine help in muscle contraction?

Answer 12

Acetylcholine collects in the junctional folds, binds to nicotinic receptors, and elicits muscle contraction. (neuromuscular junction)

Question 13

How are transmitter-gated ion channels unique?

Answer 13

If there is no transmitter bound to the receptor then the ion channel remains closed and impermeable to ions.

Question 14

How does a NT approach the transmitter-gated ion channels?

Answer 14

The neurotransmitter causes a change in the shape of the subunits that form the channel allowing certain ions to pass.

Question 15

How do Excitatory Post-Synaptic Potentials occur?

Answer 15

1. Neurotransmitter binds to receptors which opens ion channels.
   
   2. The influx of Na+ into the postsynaptic cell will depolarise Vm towards Threshold.
   3. This is called an Excitatory Postsynaptic Potential (EPSP).

Question 16

How do Inhibitory Post-Synaptic Potentials occur?

Answer 16

1. Neurotransmitter binds to receptors which changes the conformation of the receptors and opens ion channels.
   
   2. The influx of Cl– into the postsynaptic cell will repolarise Vm towards rest.
   3. This is called an Inhibitory Postsynaptic Potential (IPSP).

Question 17

How do NTs approach metabotropic receptors?

Answer 17

Neurotransmitters bind to receptor, but instead of immediately opening ion channel, the activation of a G-coupled protein must occur first

* The G protein can influence the opening of ion channels
* The G protein can additionally affect enzymes, and activate second messengers which initiates signalling cascades

Question 18

What is the basic structure of metabotropic receptors?

Answer 18

The receptor consists of 7 transmembrane spanning alpha helices.

Question 19

What is the basic structure of a G-protein?

Answer 19

G-Proteins consist of 3 subunits: α, β and γ.

Question 20

How are G-proteins then activated?

Answer 20

When neurotransmitter binds to the receptor it changes shape in a way that catalyses the release of guanosine diphosphate rom the α subunit

GDP is replaced by GTP which causes the alpha subunit to break apart from the β and γ subunits.

The subunits then interact with other intracellular proteins to transmit signals.

Question 21

How is a metabotropic receptor activated then?

Answer 21

When neurotransmitter binds to the receptor, it causes the GDP to be replaced by guanosine triphosphate (GTP)

Question 22

How is the metabotropic receptor inactivated?

Answer 22

• The translocation of GTP to the G-protein causes the Gα subunit plus GTP to split from the Gβγ complex.
  
  • The Gα subunit terminates its own activity by converting the bound GTP back into GDP thereby causing the Gα and Gβγ subunits to rejoin.

Question 23

How are b noradrenergic receptor activated?

Answer 23

1. NE (or noradrenaline) binds to the receptor and activates the G-protein.
   
   2. The G-protein activates the effector protein, adenylyl cyclase
   3. Adenylyl cyclase uses ATP to produce cyclic adenosine monophosphate (cAMP), a second messenger.
   4. Cyclic AMP activates a protein kinase
   5. Some protein kinases can close K+ channels through a process known as phosphorylation

Question 24

What is phosphorylation?

Answer 24

Protein kinases like to add phosphate groups to things through a process called phosphorylation.

Phosphorylation of particular channel subunits can change the shape or conformation of the channel

Question 25

How is synaptic transmission stopped?

Answer 25

1. Enzymatic Degradation 2. Reuptake into Terminal 3. Uptake by Glial Cells

Question 26

How does the neuron differentiate from thousands patterns?

Answer 26

A single neuron integrates many thousands of inputs. This pattern of activity determines whether the cell will spike.

Question 27

How does a EPSP generate an action potential?

Answer 27

* A single EPSP is usually much too small to make a neuron fire an action potential. * EPSPs have to be summed together to bring a neuron to ring threshold. * Activity across space and time is additive.

Question 28

How do EPSPs generate a large synaptic response?

Answer 28

* Activation of a single synapse generates a small amplitude EPSP. * Activation of multiple inputs simultaneously generates a much larger postsynaptic response.

Question 29

In what way can EPSP generate a large synaptic response with a single synapse?

Answer 29

* Activation of a single synapse generates a small amplitude EPSP * Activating the same synapse in rapid succession generates a much larger postsynaptic response.

Question 30

How can IPSPs affect EPSPs?

Answer 30

* IPSPs can cancel-out the excitatory effects of EPSPs. * Activation of an inhibitory synapse hyperpolarises Vm. * temporal summation cannot overcome the effects of the prior IPSP * A hyperpolarising IPSP makes it more difficult for excitatory inputs to bring Vm to threshold. * inhibitory interneurons often make axoaxonic synapses close to the axon hillock.

Question 31

How do IPSPs act as an electrical shunts?

Answer 31

* The EPSP recorded at the active synapse is large in amplitude. * EPSP loses much of its “punch” with distance. * A tonically active inhibitory synapse would drive Cl– inwards and K+ outwards as the EPSP approached.

Question 32

What can happen to the synaptic potentials with distance?

Answer 32

They decay passively en route to the soma

Question 33

As the potential is decaying, how is the message conveyed?

Answer 33

Both diffusion and electrostatic pressure drive electric current along the inside of the dendrite. Some of the electric current leaks out of the cell. Synapses close to the soma have the biggest impact.

Question 34

How are electric currents so easily able to slip out in to the cells?

Answer 34

• Dendrites have no voltage-gated Na+ or K+ channels and no myelin sheath. • The length constant is shaped by two factors: 1.  Internal Resistance (such as the diameter of the dendrite). 1.  Membrane Resistance (open channels in the membrane that allow current to leak out)