Neurotransmitters and synaptic integration

Question 1

What is synaptic integration ?

Answer 1

Used to describe how neurons ‘add up’ these inputs before the generation of a nerve impulse, or action potential

Question 2

What are the our principal stages of chemical transmission:

Answer 2

1. synthesis of a transmitter substance
2. storage and release of the transmitter
3. the transmitter’s interaction with a postsynaptic receptor
4. removal of the transmitter from the synaptic cleft

Question 3

What are the two different neurotransmitter types ? and what are the effects of both ?

Answer 3

1. amino acids
   or derivatives - packaged into small clear synaptic
   vesicles
   - influence excitability
2. Neuroactive peptides: amino acid polymers packaged in large dense-core vesicles (DCVs)
   - more diverse effects (gene expression, synaptogenesis, morphology etc.)
   many can act as hormones on distant targets but also neurotransmitters

Question 4

How does release of neuroactive peptides from DCVs differ from small molecule neurotransmission ?

Answer 4

• peptide and DCVs synthesised at the soma
• exocytosis is not highly regulated and does not require an active zone; vesicle membrane is
  used only once.
• while synaptic vesicle release is associated with fast, sustained transmission, DCV release is not

Question 5

How do small synaptic vesicles refill ?

Answer 5

Refilling occurs at the terminal itself and

requires ATP

Question 6

What is this required ATP used by?

Answer 6

The ATP is used by a vesicle-ATPase (v-ATPase) to concentrate H+ ions inside the vesicle using the energy generated by the hydrolysis of cytoplasmic ATP

Question 7

What is the H+ ion gradient used to drive?

Answer 7

• This H+ gradient is then used to drive exchange of H+ ions for neurotransmitter (2 protons per NT molecule)
  using a special transporter protein
• The transporter doesn’t have a pore - it actively
  transports NT across the membrane

Question 8

Transmitters are removed by three

main processes:

Answer 8

• diffusion of NT away from the cleft
• degradation (only ACh)
• reuptake

Question 9

What is the role of neurotransmitter reuptake?

Answer 9

1. Terminates the action of the transmitter

2. Recaptures transmitter for reuse

Question 10

What is reuptake carried and driven by ?

Answer 10

Carried by specific transporter molecules driven by the electro-chemical potential provided by
the Na+, K+ and Cl- gradients

Question 11

How can reuptake effect drug target ?

Answer 11

• Cocaine blocks norepinephrine re-uptake
• Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) block serotonin reuptake
• In this way, the NT remains in the cleft for
  longer to exert a transmission effect

Question 12

Explain signalling of gas nitric oxide ?

Answer 12

• NO is a small, highly-diffusible molecule that is synthesised at source
  from arginine by the cytoplasmic enzyme nitric oxide synthase (NOS)
• The target receptor is soluble guanylyl
  cyclase (sGC) which mediates the
  production of cGMP from GTP

Question 13

What are gaseous neurotransmitters thought to act as ?

Answer 13

Retrograde messenger - transmission from target neurons backwards
across chemical synapses

Question 14

Where does synaptic integration occur ?

Answer 14

At the axon initial segment (axon hillock)

Question 15

Why are action potentials not generated at the synapse ?

Answer 15

Because the axon hillock has few voltage-gated channels important for spike activation

Question 16

What does the axon hillock contain ?

Answer 16

The spike-initiating zone, a region where firing threshold is around +10mV above resting potential versus +30mV at the cell body

Question 17

Neuronal integration results from ?

Answer 17

The passive spread of
synaptic potentials to the
trigger zone

Question 18

What is the passive spread influenced by?

Answer 18

Two passive membrane 
properties:
1. The length constant – how far 
an input ‘gets’ before it 
decays
2. The time constant – how long 
an input ‘lasts’ before it 
decays

Question 19

What is important at the spike initiation zone ?

Answer 19

The size of the response

Question 20

What are two different types of summation ? and explain ?

Answer 20

Temporal summation occurs when a single pre-synaptic neuron fires many times in succession, causing the post-synaptic neuron to reach its threshold and fire. Spatial summation occurs when excitatory potentials from many different pre-synaptic neurons cause the post-synaptic neuron to reach its threshold and fire.