The Roles of Neurones and Glia

Question 1

What are the different types of glia cells?

Answer 1

Astrocytes
- Most abundant type of glial cell
- Supporters
Oligodendrocytes
- Insulators
Microglia
- Immune response

Question 2

What is the role of astrocytes?

Answer 2

Structural support
Help provide nutrition for neurones
- Glucose-lactate shuttle
Remove neurotransmitters (uptake)
- Control concentration of neurotransmitters
   (especially important for glutamate (toxic))
Maintain ionic environment
- K+ buffering
Help to form blood brain barrier
- (Only help, don't actually form it)

Question 3

Explain how astrocytes provide nutrition for neurones.

Answer 3

Neurones do not store or produce glycogen
There fore Astrocytes produce lactate which can be transferred to neurones
- Supplements their supply of glucose
Known as the glucose-lactate shuttle
Astrocytes receive glycogen and convert it to lactate before transferring it to neurones

Question 4

Explain how astrocytes help to remove neurotransmitters.

Answer 4

Astrocytes have transporters for transmitters such as glutamate, and they help to keep the extracellular concentration low

Question 5

Explain how astrocytes help to buffer K+ in brain ECF.

Answer 5

Due to lots of action potentials, local concentrations of K+ ions can increase

Astrocytes have incredibly low membrane potentials (near potassium equilibrium potential)

So they can take up K+ and reduce local concentrations of K+

Up to a point (Can’t go more than 12mM of K+)

Question 6

What is the role of an Oligodendrocytes?

Answer 6

Responsible for myelinating axons in CNS

Compare with PNS where Schwann cells are responsible for myelination

Question 7

What do microglia do?

Answer 7

Immunocompent cells
Recognise foreign material - when activated
Phagocytosis to remove debris and foreign material
Brain’s main defence system

Question 8

What is the purpose of the blood brain barrier?

Answer 8

Limits the diffusion of substances from the blood to the brain extracellular fluid
Maintains the correct environment for neurones
Concentration of substances transported can be controlled

Question 9

How is the blood brain barrier maintained?

Answer 9

Capillaries have:

• Tight junctions between endothelial cells
• Basement membrane surrounding capillary
• End feet of astrocyte processes
  
  • (Sending messages to endothelium to form tight
    junctions. … maybes)

Question 10

What are transported across the blood brain barrier?

Answer 10

Substances such as glucose and amino acids and potassium

Question 11

What is special about the CNS immune system?

Answer 11

It is immune privileged (immune specialised)
Does not undergo rapid rejection of allografts

Rigid skull will not tolerate volume expansion
- Too much inflammatory response would be harmful
Microglia can act as antigen presenting cells

T-cells can enter the CNS

CNS inhibits the initiation of the pro-inflammatory T-cell response

Question 12

How do neurones communicate?

Answer 12

Synapses

Question 13

Give a brief overview of what happens at a synapse

Answer 13

Depolarisation in the terminal opens voltage-gated Ca2+ channels.
Ca2+ ions enter the terminal

Vesicles of neurotransmitter fuse and release the neurotransmitter into synaptic cleft

Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane

There is then an inactivation method for getting rid of the neurotransmitter but this depend son the neurotransmitter

Question 14

What are the different postsynaptic responses?

Answer 14

Depends on:

• Nature of neurotransmitter
• Nature of receptor

Ligand-gated ion channel
G-protein coupled receptor

Question 15

Give an overview of the different types of neurotransmitters.

Answer 15

> 30 neurotransmitters have been identified in the CNS

Can be divided into three chemical classes:
Amino Acids
- Glutamate, GABA, glycine
Biogenic Amines
- Acetylcholine, noradrenalin, dopamine, serotonin(5-HT),
Peptides
- Dynorphin, enkephalins, substance P, somatostatin

Question 16

Name some amino acid neurotransmitters.

Answer 16

Excitatory amino acids

• Mainly glutamate
• Major excitatory neurotransmitter
  
  • Over 70% of all CNS synapses are glutamatergic
  • Present throughout the CNS

Inhibitory amino acids

• GABA
• Glycine

Question 17

What are the different glutamate receptors?

Answer 17

IONOTROPIC
Ion channel - permeable to Na+ and K+ (and in some cases Ca2+ ions)
Activation causes depolarisation
- AMPA receptors (Na+/K+)
- Kainate receptors (Na+/K+)
- NMDA receptors (Na+/K+ and Ca2+)

METABOTROPIC
- mGluR1-7
G-protein coupled receptor
Linked to either:
- Changes in IP3 and Ca2+ mobilisation
- Or inhibition of adenylate cyclase and decreased cAMP 
   levels

Question 18

Tell me about Glutamatergic synapses

Answer 18

Glutamatergic synapses have both AMPA and NMDA receptors
AMPA receptors mediate the initial fast depolarisation
NMDA receptors are permeable to Ca2+
BUT
NMDA receptors need glutamate to bind AND the cell to be depolarised to allow an ion to flow through the channel (Mg2+ blocks this channel until conditions met)
- Also glycine acts as a co-agonist

Question 19

Tell me about glutamate receptors and synaptic plasticity.

Answer 19

Glutamate receptors have an important role in learning and memory
- Activation of NMDA receptors (and mGluRs) can up-
regulate AMPA receptors
- Strong, high frequency stimulation causes long term
potentiation (LTP)
- Ca2+ entry through NMDA receptors important for
induction of LTP

Question 20

How can glutamate receptors lead to excitotoxicity?

Answer 20

Too much Ca2+ entry through NMDA receptors causes excitotoxicity
- Too much glutamate - excitotoxicity

Question 21

Tell me a bit about inhibitory amino acids.

Answer 21

GABA is the main inhibitory transmitter in the brain

Glycine acts as an inhibitory neurotransmitter mostly in the brainstem, and spinal cord

The receptors of these have integral Cl- channels
Opening the Cl- channel causes hyperpolarisation
- Inhibitory post-synaptic potential (IPSP)
- Decreased action potential firing

Question 22

Tell me about some substances that can bind to GABAa receptors.

Answer 22

Barbiturates and benzodiazepines bind to GABAa receptors
Both enhance the response to GABA
- Barbiturates - anxiolytic and sedative actions, but not
used for this now
- Risk of fatal overdose also dependence and tolerance
- Sometimes used as anti-epileptic drugs
- Benzodiazepines
- Have sedative and anxiolytic effects
- Used to treat anxiety, insomnia and epilepsy

Question 23

Tell me a bit about Acetylcholine as a neurotransmitter.

Answer 23

ACh
- Neuromuscular junction
- Ganglion synapse in ANS
- Postganglionic parasympathetic
ACh is also a central neurotransmitter
- Acts at both nicotinic and muscarinic receptors in the
brain
- Mainly excitatory
- Receptors often present on presynaptic terminals to
enhance the release of other transmitters

Question 24

What are some conditions associated with dopamine dysfunction?

Answer 24

Parkinson’s disease
- Associated with loss of dopaminergic neurones
- Substantia nigra input to corpus striatum
- Can be treated with levodopa - converted to dopamine
by DOPA decarboxylase (AADC)
Schizophrenia
- Maybe due to release of too much dopamine
- Amphetamine releases dopamine & noradrenaline
- Produces schizophrenic like behaviour
- Antipsychotic drugs are antagonists at dopamine D2
receptors

Question 25

Tell me about Noradrenaline as a neurotransmitter.

Answer 25

Transmitter at postganglionic effector synapse in ANS

Also acts as a neurotransmitter in CNS
Operates through G-protein coupled alpha- and beta- adrenoceptors
Receptors to noradrenaline in the brain are the same as in the periphery

Most NA in the brain comes from a group of neurone in the locus ceruleus
- LC neurones inactive during sleep
- Activity during behavioural arousal
- Amphetamines increase release of noradrenaline and
increase wakefulness
Relationship between mood and state of arousal
- Depression may be associated with a deficiency of NA