Synapses

Question 1

What are the 3 stages of synaptic activity?

Answer 1

1. Presynaptic activity
2. Postsynaptic activity
3. Neurotransmitter inactivation (so signals can be turned off)

Question 2

What two types of presynaptic mechanisms are there?

Answer 2

• Small molecule transmitters

- Peptide/large molecule transmitters

Question 3

How do small molecule transmitters of the synapse work?

Answer 3

• Enzyme moves down the axon to the bouton
• Enzyme activates precursor into active form and packages it into a vesicle
• Vesicles release neurotransmitters on demand at the synaptic cleft
• Precursors are reformed and reuptaken to be repacked into active enzymes

Question 4

How do peptide/large molecule transmitters of the synapse work?

Answer 4

• Neurotransmitters/precursors are made and packaged in the cell body ( since molecules are bigger)
• They move down the axon in vesicles via the microtubule tracks
• Enzymes modify the precursors to produce peptide neurotransmitters
• Neurotransmitters are released on demand
• They are not taken up again, but they are degraded/recycled by the glial cells

Question 5

What happens to the vesicles after releasing the neurotransmitters?
How do we now?

Answer 5

After fusion, the vesicles are recycled

In an experiment, the boutons were placed into Horseradish Peroxidase (HRP)

• Vesicles started to form in the bouton, containing HRP
• These vesicles started to fuse together to form an even bigger structure, endosome
• The endosome was then recycled into many other vesicles, so all of these then contained HRP

Question 6

What are the stages of new vesicle formation?

Answer 6

1. Budding - new vesicles form from the endosome
2. Storage - vesicles get linked together by glycoproteins & they are combined to parts of the cell wall
3. Docking - back-up storage in case there is a large demand for neurotransmitters
4. Priming - vesicles are pulled close proximity to the end-membrane
5. Calcium entry - causes the vesicle and end-membrane to fuse together
6. Fusion - membranes fuse, neurotransmitters are released

Question 7

Name the glycoproteins and decribe their behaviour during docking, priming and release of neurotransmitters

Answer 7

Synaptotagmin, Synaptobrevin, Syntaxin and SNAP-25

• Syntaxin and SNAP-25 are attached to the membrane, Synaptotagmin and Synaptobrevin are attached to the vesicle
• Synaptobrevin, Syntax and SNAP-25 join into a helical structure
• Entering Ca+ joins to Synaptotagmin
• Calcium bound Synaptotagmin catalyses membrane fusion

Question 8

What are ionotropic receptors?

How do they work?

Answer 8

Ligand gated ion channels

• When transmitters bind to their receptors, they cause a conformational change, creating a pore at the middle of the channel
• Ion selective: selective about ion size and about ion charge
• The passage of ions in and out changes the voltage of the cell, either to depolarise or hyperpolarise

Question 9

What are metabotropic receptors?

How do they work?

Answer 9

G-protein coupled receptors

• When transmitter binds to receptor, the inner membrane part of the receptor undergoes a conformational change
• G-protein binds to the receptor in the cytoplasm, getting rid of GDP and picking up GTP/becomes phosphoralysed and splits into two parts (active/non-active)
• GTP and G-protein can bind to the membrane bound enzyme, creating a lot of messenger molecules
• Amplification process: these messenger molecules then can activate many channels OR they can join nuclear transcription to create more proteins for channels/receptors
• GTP sheds a Phosphate, changing the conformation of the G-protein again + ion channel is closed because messengers are broken down
• G-protein dissociates from the enzyme and no more messengers are produced
• G-protein recombines with its other part and wants to join to the receptor again but can’t, because neurotransmitter is not bound to it so there is no conformational change for the receptor

Question 10

What are the two post-synaptic responses?

Describe them

Answer 10

Excitatory (EPSP)
- A net flow of positive ions flowing into the cell that depolarises the membrane, but causing an action potential very rarely (Na+)

Inhibitory (IPSP)
- A net flow of negative ions flowing into the cell that hyperpolarises the cell (Cl-)

• both take about 8 msec because the ions leak out
• due to the long time, lots of small depolarisations can pile up to produce an action potential

Question 11

Describe the 3 types of summations of neurotransmissions

Why are EPSPs able to summate?

Answer 11

Single EPSP
- quanta release of neurotransmitters

Spatial summation
- Simultaneous release of more than one neurotransmitter on different axons

Temporal summation
- Neurotransmitters are released over a short range of time on the same axon

They are able to summate because they have no refractory period

Question 12

How do EPSPs and IPSPs work together?

Answer 12

• Two excitatory post-synaptic potentials will reach the threshold and will create an action potential
• One EPSP and one IPSP will cancel each other out
• Two EPSPs and one IPSP will reach the threshold but there will be no action potential

Question 13

What are the three functions of the chemical synapse?

Answer 13

Computation
- As automatic summation of multiple PSPs is required to achieve threshold, integration acts as a decision making process based on EPSP and IPSP input
(All info merges into one)

Rectification
- As chemical inpulses transmit information in one direction only, this rectification serves to channel information (Helps channel output info into input info of another neuron)

Plasticity
- Controlled changes in the amount of transmitters released, the number of receptors present and the efficiency of the inactivation process provide a mechanism for adaptive plasticity (LTP and LTD); involved in learning and memory; (up or down regulation)

Question 14

What are the roles of IPSP in the nervous system? Give two examples

Answer 14

Fine tuning movements
- IPSP/inhibition helps stop and control movement

Pain modulation

• Sensory pain neuron synapses with the ascending pain neuron, letting your brain know you are in pain
• To dumb down the pain, a descending pain modulation enhances and therefore increases the inhibitory effect of an inhibitory interneuron on the ascending pain neuron

Question 15

Describe synaptic plasticity in memory and learning

Answer 15

• You are able to form memories and learn new things when you have stronger signals
• Stronger synaptic connections mean easier and better synaptic transmission
• Stronger synaptic connections come from more vesicles, greater excitability, more receptors and more parallel synapses

Question 16

How does addiction arise?

Answer 16

Addiction is caused by the attenuation/loss of transmission through over-stimulation of a pleasure
pathway with a reduced vesicle/receptor response

1. Overstimulated
2. Transmission/vesicle number or reception/receptor number decreased
3. More over-stimulation
4. Further attenuation
5. Even more over-stimulation

Question 17

What is neuronal convergence?

Give an example

Answer 17

• Many come into one
• The more dendrites a neuron has, the higher the degree of convergence
• e.g.: eye cells, many cones (B&W, detecting movement) become cone bipolars, which synapse onto one ganglion cell

Question 18

What is neuronal divergence?

Give an example

Answer 18

• Information from a single neuron is passed to a number of other neurons simultaneously and without loss of signal strength
• Can be spatially focused (few neurons, to specific locatons) or widely divergent (to a wide number of locations)
• e.g.: knee jerk reflex
  1. Stimulating the patellar tendon of the knee results in a signal travelling up from the muscle spindle through the dorsal root ganglion into the cortex
  2. The signal can either continue onto an excitatory pathway, through which it constricts the extensor muscle
  3. Or it can continue on excite an inhibitory neuron turn off the motor neuron for the flexor muscle, relaxing it

Question 19

What is local neuronal feedback?

Answer 19

Feedback is when one neuron passes a signal to a second neuron, which has an axonal
branch back to the first neuron, thus moderating the action of neuron 1 by negative
feedback
e.g.: cortical neurons sending commands to spinal motorneurons which receive feedback from sources such as the visual system or somatosensory system (feeling, sensation) and then it produces motor output (that is crude but then refined by using the feedback from the other systems)