Session 2: The Role of Neurones and Glia Flashcards

1
Q

Types of glial cells.

A

Astrocytes

Oligodendrocytes

Microglia

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2
Q

Functions of oligodendrocytes

A

Insulators providing the myelin sheath for axons

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3
Q

Functions of the microglia.

A

Immune response

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4
Q

The role of the astrocytes.

A

Structural support for neurons

Help to provide nutrition for neurones via the glucose-lactate shuttle.

Removal of neurotransmitters by taking up glutamate.

Maintain ionic environment by K+ buffering.

Help to form the blood brain barrier.

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5
Q

Explain the energy provision to neurones by astrocytes.

A

Can be either by a direct pathway where glucose goes from blood into neuron directly.

or

By glucose lactate shuttle where glucose enters the astrocyte and is formed into glycogen.

The glycogen then turns into pyruvate and then into lactate.

The lactate then is transported out of the astrocyte and into the neuron where the lactate is transformed into pyruvate again.

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6
Q

Explain astrocytes removal of neurotransmitters.

A

They have transporters for transmitters and especially glutamate.

Glutamate is toxic in high concentrations which means that it needs to be taken up somehow and that is done via the astrocytes.

This helps to keep the extracellular concentration low.

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7
Q

Explain how astrocytes work as buffers for K+ in the brain ECF.

A

As neuronal activity increases in the brain there will be an influx of Na+ and to combat that influx there is an efflux of K+.

This leads to a rise of K+ extracellularly and hyperkalaemia can ensue. In order to compensate for this rise in K+ the astrocytes will take up K+.

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8
Q

How does myelination increase conduction velocity?

A

By a large increase in membrane resistance

By a large decrease in membrane capacitance

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9
Q

What is capacitance?

A

The membrane’s ability to store charge

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10
Q

Explain the role of microglia.

A

Immunocompetent cells which recognise foreign material.

This causes phagocytosis to remove debris.

This is the brain’s main defence.

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11
Q

Explain the purpose of the blood brain barrier.

A

Limits the diffusion of substances from the blood to the brain ECF.

It maintains the correct environment for the neurones.

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12
Q

Explain the relation between the brain capillaries and the blood brain barrier.

A

There are tight junctions between the endothelial cells.

There is also a basement membrane surrounding the capillaries.

And end feet of astrocyte processes.

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13
Q

Give examples of substances that can be transported across the BBB.

A

Glucose

Amino acids

Potassium

CO2

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14
Q

Explain the typical neuronal structure.

A

Four main sections:

Cell soma

Dendrites

Axon

Terminals

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15
Q

Briefly explain the neurotransmitter release at the synapse.

A

Depolarisation causes Ca2+ ions to enter the terminal.

The Ca2+ causes the vesicles to fuse with the membrane and release the transmitters.

The neurotransmitters diffuses acrsos the synaptic cleft and binds to receptors on the postsynaptic membrane causing an action potential.

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16
Q

What does the postsynaptic response depend on?

A

The neurotransmitter

The receptor (ligand-gated or g-protein)

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17
Q

What are the main groups of neurotransmitters in the CNS?

A

Amino acids

Biogenic amines

Peptides

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18
Q

Give example of NT amino acids.

A

Glutamate

GABA

Glycine

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19
Q

Give examples of NT biogenic amines.

A

ACh

NA

Dopamine

Serotonin

Histamine

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20
Q

Give examples of NT peptides

A

Substance P

Somatostatin

Cholecystokinin

Neuropeptide Y

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21
Q

Give examples of excitatory amino acids as NTs.

A

Mainly glutamate

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22
Q

Give examples of inhibitory amino acids NTs.

A

GABA

Glycine

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23
Q

Give examples of the main glutamate receptors.

A

Ionotropic receptors

Metabotropic receptors

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24
Q

Give the subreceptors of ionotropic glutamate receptors.

A

AMPA receptors

Kainate receptors

NMDA receptors

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25
Q

Explain how the ionotropic receptors work.

A

They are ion channels receptors and cause an increase in the permeability of Na+ and K+ (also Ca2+ in the case of NMDA receptors).

This causes depolarisation and increased excitability.

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26
Q

Explain how the metabotropic receptors work.

A

G-protein coupled receptors

Ip3 and Ca2+ increase

or

inhibition of adenylate cyclase and decreased cAMP.

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27
Q

Explain the fast excitatory reponses.

A

Excitatory neurotransmitters cause depolarisation of the postsynaptic cleft by acting on ligand-gated ion channels (ionotropic).

This causes excitatory postsynaptic potential (EPSP) and the depolarisation causes more action potentials

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28
Q

What kind of receptors are found on glutamatergic synapses?

A

They have both AMPA and NMDA receptors.

The AMPA receptors mediate the initial fast depolarisation and the NMDA receptors are permeable to Ca2+.

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29
Q

Explain how the NMDA receptors work.

A

The receptors need glutamate to bind and the cell to be depolarised to allow ion flow through the channels.

It also works with glycine as a co-agonist.

30
Q

Explain the glutamate receptors role in learning and memory.

A

There is activation of NMDA receptors which can up-regulate the AMPA receptors.

The strong and high frequency of stimulation causes a long term potentiation called LTP.

Ca2+ entry through NMDA receptors are important for induction of LTP.

31
Q

In the case of too much Ca2+ entry through the NMDA receptors, what may happen?

A

It can cause excitotoxicity by too much glutamate.

32
Q

What is the main inhibitory transmitter in the brain? (AA)

A

GABA

33
Q

Where does glycine act as an inhibitory NT?

A

Mostly in brainstem and spinal cord.

34
Q

Explain how the GABA and glycine receptors work.

A

They have integral Cl- channels which when they open causes hyperpolarisation and an inhibitory post-synaptic potential and a decrease in action potential firing.

35
Q

Give examples of drugs that bind to GABA (A) receptors.

A

Barbiturates and Benzodiazepines.

36
Q

Explain the action of barbiturates.

Risks as well

A

Enhance the response to GABA.

They have an anxiolytic (inhibits anxiety) and sedative action. Not really used for it but can be used as an anti-epileptic drug.

There is a risk of fatal overdose

Dependence

Tolerance

They have largely been replaced by benzodiapezines

37
Q

Explain the action of benzodiapezines.

A

Enhance the response to GABA

Sedative and anxiolytic effects that is used to treat anxiety, insomnia and epilepsy.

38
Q

What releases glycine?

A

Inhibitory interneurones in the spinal cord.

39
Q

What role do other amino acid transmitters have that are not glutamate, GABA or glycine?

A

Modulatory role and discreet pathways.

40
Q

Where does ACh act?

A

Neuromuscular junction

Ganglion synapse in ANS

Postganglionic parasympathetics

Central neurotransmitter

Nicotinic and muscarinic receptors in the brain

It is mainly excitatory and the receptors often present on the presynaptic terminals to enhance the release of other transmitters.

41
Q

Explain briefly the cholinergic pathways in the CNS.

A

They originate in the basal forebrain and brainstem.

They then give diffuse projections to many parts of the cortex and hippocampus.

E.g. Septohippocampal pathway.

42
Q

What are local cholinergic interneurones?

A

Found in the CNS and are not pathways but act locally like the corpus striatum.

43
Q

What are the cholinergic pathways mainly involved in?

A

Arousal

Learning

Memory

Motor control

44
Q

Explain how Alzheimer’s disease relate to cholinergic pathways.

A

Degeneration of cholinergic neurones in the nucleus basalis.

45
Q

What is used to alleviate symptoms of Alzheimer’s disease?

A

Cholinesterase inhibitors

46
Q

Give examples of dopaminergic pathways in the CNS.

A

Tubero-hypophyseal pathway

Nigrostriatal pathway

Mesocortical pathway

Mesolimbic pathway

47
Q

Main function of nigrostriatal pathway.

A

Involved in motor control (substantia nigra to dorsal striatum)

48
Q

Main function of the mesocortical pathway.

A

Involved in mood, arousal and reward.

49
Q

Main function of the mesolimbic pathway.

A

Involved in mood, arousal and reward.

50
Q

Give examples of conditions associated with the dopamine pathway.

A

Parkinson’s

Schizophrenia

51
Q

Briefly explain Parkinson’s diease.

A

Associated with loss of dopaminergic neurones.

This is at the input of substantia nigra (pars compacta) to the corpus striatum.

52
Q

What is Parkinson’s treated by?

A

Levodopa

L-dopa is converted in to the desired dopamine via DOPA decarboxylase also called AADC

53
Q

Explain how schizophrenia can be related to dopamine.

A

May be due to release of too much dopamine.

Amphetamine releases dopamine and NA.

This produces schizophrenic like behaviour.

54
Q

What is given in the case of Schizophrenia?

A

Antipsychotic drugs such as Dopamine D2 receptor antagonists.

55
Q

Carbidopa is a drug that is given to inhibit AADC from converting L-DOPA into Dopamine, why is this given in Parkinson’s?

A

Because Carbidopa only inhibits L-Dopa conversion into Dopamine outside of the BBB.

This is because you don’t want L-DOPA to be converted outside of the brain ECF.

56
Q

Why does carbidopa not convert L-DOPA into Dopamine in the brain?

A

Because it cannot cross the BBB

57
Q

Roles of noradrenaline (NA)

A

Transmitter at postganglionic at effect synapse in ANS

NT in CNS

Acts via GPCRs and alpha+beta adrenoceptors.

Receptors in the brain for NA is the same as in the PNS.

58
Q

Briefly explain the noradrenergic pathways in the CNS.

A

Cell bodies of NA containing neurones are found (arise) from the brainstem and specifically pons and medulla.

There is then a diffuse release of NA throughout the cortex, hypothalamus, amygdala, and cerebellum.

59
Q

Where does most of the noradrenline in the brain come from?

A

A group of neurones in the locus ceruleus.

60
Q

Give examples of how the locus ceruleus neurones can differ in activity.

A

Inactive during sleep

Increased activity during behavioural arousal

Increased activity due to amphetamines. (Also increase dopamine release)

61
Q

Expain the relationship between mood and state of arousal.

A

Depression may be associated with a deficiency of NA.

62
Q

Briefly explain the Serotonergic pathways in the CNS.

A

Serotonin and 5-HT have a similar distribution to noradrenergic neurones.

The functions are sleep/wakefuness and mood.

63
Q

Give example what can be given in treating depression and anxiety disorders relating to the serotonergic pathways.

A

SSRIs (Serotonin selective reuptake inhibitors)

64
Q

What structure produces dopamine?

A

Substantia nigra

65
Q

What structure produces serotonin?

A

raphe nuclei

66
Q

What structure produces noradrenaline?

A

Locus coeroleus

67
Q

Explain glycine’s role in the patellar tendon reflex.

A

Hitting the patellar tendon causes spindle fibres to activate and afferents activate with glutamate as their NT. This produces an excitatory response of the quadriceps to jerk the knee upwards (knee extension).

Glutamate also excites an interneuron in order to activate it and produce glycine at another synapse which will inhibit the hamstring muscle causing it to relax in order to not produce the opposing force.

68
Q

Explain how glutamate can cause excitotoxicity through NMDA receptors.

A

NMDA receptors activate and cause an influx of Ca2+.

Too much Ca2+ can be damaging to the cell and cause it to die.

As the cell dies it will release a substantial amount of potassium which will circulate freely in the ECF now causing an increased concentration.

This causes an increase in K+ in ECF and will cause easier depolarisation of adjacent neurons. This depolarisation will activate NMDA receptors in other places and more cells will die. This leads to a spread of excitotoxicity.

69
Q

Explain how NMDA receptors are activated.

A

NMDA receptors are not solely activated by glutamate.

Glutamate will bind to the NMDA receptors but magnesium will be stuck in the pore of the ion channel.

Prolonged depolarisation of the cell and AMPA receptors will eventually remove the magnesium from the NMDA pore in order to let Na+ and Ca2+ to move into the cell.

70
Q

Briefly explain the CNS immune response.

A

It does not undergo any rapid rejection of a foreign object as that would be harmful for the brain.

No inflammatory response happens because the brain would not be able to tolerate an increased volume.

The microglia can act as antigen presenting cells and present antigen to T-cells which can enter the CNS.

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