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Y2 - CNS > Lecture 3 - Cellular Physiology Of The Brain > Flashcards

Lecture 3 - Cellular Physiology Of The Brain Flashcards

1
Q

What are the 2 main cellular components of the nervous systems?

A

Neurones
Supporting glia

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2
Q

What are the 3 major types of glia in the CNS?

A

Astrocytes
Oligodendrocytes
Microglia

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3
Q

What is the main overall function of glial cells?

A

Nourish neurones
Insulate neurones
Remove waste

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4
Q

What is the most abundant type of glial cell?

A

Astrocyte

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5
Q

What are the roles of Astrocytes?

A

Structural support
Nutritional support
Re-uptake of neurotransmitters
Maintain ion conecentrations in Extracellular fluid
Contributes to BBB
Help repair neural damage

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6
Q

How do Astrocytes provide nutritional support to the CNS?

A

Converts glucose to lactate so that it can be transferred into the neurones

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7
Q

What is the pathway for carbohydrate uptake into neurones?

A

Glucose into Astrocyte via GLUT3
Then converted into lactate
Lactate transported into neurone via MCT1

Or

Glucose transported by GLUT1 in apical and basal surface of endothelial cell to interstitial space
Glucose then transported from interstitial space to neurone by GLUT3 in neuorlemma

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8
Q

Why is it important that Astrocytes re take up neurotransmitters?

A

Sometimes they leak out of synapses

This could lead to excessive activation of receptors

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9
Q

Which ion concentration in particular has its concentration controlled by the Astrocytes in the extracelllar fluid?

A

Potassium since it’s released in. Large quantities in highly active areas of brain

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10
Q

How do Astrocytes contribute to the blood brain barrier?

A

Induce expression of tight junctions. Between brain and endothelial cells

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11
Q

How are gap junctions between. Astrocytes important?

A

Forms a syynctium allowing calcium waves to propagate through all of the Astrocytes which may help with cognitive function

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12
Q

How many synapses do Astrocytes form?

A

3

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13
Q

What is the main function of Oligodendrocytes?

A

Myelination of neurones in the Central Nervous System

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14
Q

What cells myelinate neurones of the PNS?

A

Schwann cells

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15
Q

What cell is damaged in multiple sclerosis?

A

Oligodendrocytes

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16
Q

What is an example of a neurodegernative disorder that affects schwann cells? (PNS)

A

Guillain-Barre Syndrome

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17
Q

What is the main function of microglia?

A

Major immune cell in the CNS

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18
Q

What type of immune cell do Microglial resemble the most to protect the brain?

A

Macrophages

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19
Q

How does a Microglial cell appear when inactivated?

How do they appear when activated?

A

Branched appearance with their process scanning for antigens

When activated (inflammation) they become phagocytose like a macrophage

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20
Q

What positive and negative affects do Microglia have?

A

Remove debris and clean up site of damage

Negative is that they may cause collateral damage injuring cells that were not involved int he initial. Pathology

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21
Q

What is the function of the blood brain barrier?

A

To limit diffusion of substances from the blood to the brains extracellular fluid
Maintains the correct environment for neurones

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22
Q

What makes up the blood brain barrier at the brain capilarries?

A

Tight junctions between endothelial cells
Basement membrane surround capilary
End feet of Astrocyte processes

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23
Q

What are some substances that can cross the blood brain barrier?

A

Glucose
Amino acids
K+

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24
Q

What is meant by CNS Immune privileged/immune specialised?

A

The specialised immune repsonse that occurs in the brain where the CNS inhibits the initiation of the pro-inflammorty T cell response

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25
Q

Why does the CNS have a specialised immune response?

A

Since a rapid inflammatory response would lead to the brain swelling leading to rapid increase in intracranial pressure leading to ischameic hypoxia and rapid death

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26
Q

What immune cells can enter the brain?

A

T cells

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27
Q

What are the 4 main sections to a typical neurone?

A

Cell soma (body)
Dendrites (projections)
Axon
Terminals

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28
Q

What happens at a synapse once the presynaptic terminal depolarises?

A

Ca2+ voltage gated ion channels open
Ca2+ influx
Ca2+ binds to vesicles containing neurotransmitter stimulating them to fuse with the presynaptic membrane and release the transmitter into the cleft
Neurotransmitter diffuses across cleft and binds to receptors on the postsynaptic membrane

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29
Q

What is the post synaptic response once an action potential reaches the presynaptic terminal?

A

Once the neurotransmitter binds to the postsynaptic receptor the response depends on the nature of the neurotransmitter and the nature of the receptor

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30
Q

What are the 2 types of receptor that can. Be on the postsynaptic membrane?

A

Ion channel (ligand gated ion channel)
G-protein coupled receptor

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31
Q

What are the 2 types of neurotransmitter?

A

Excitatory
Inhibitory

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32
Q

What is an example of an excitatory neurotransmitter?

A

Glutamate

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33
Q

What is an example of an inhibitory neurotransmiter?

A

GABA

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34
Q

What are the 3 chemical classes of neurotransmitters?

A

Amino acids
Bio genic amines
Peptides

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35
Q

What is the main excitatory amino acid neurotransmitter found all over the CNS?

A

Glutamate

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36
Q

What are the 2 main inhibitory amino acid neurotransmitters?

A

GABA
Glycine

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37
Q

What are the 2 main types of glutamate receptors?

A

Inotropic receptors (ion channel)

Metabotropic (G protein coupled receptor)

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38
Q

What is an inotropic glutamte receptor?

A

Ion channel where activation causes depolarisation if its a glutamate receptor causing cation influx

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39
Q

What is a metabotropic glutamte receptor?

A

G protein coupled receptor that’s linked to either changes in IP3 and Ca2+ Or ihbitrion of adenylate cyclase and decreased cAMP levels

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40
Q

Where is GABA a very prevalent neurotransmitter in the brain?

A

Cerbral cortex and basal ganglia

41
Q

What type of neurotransmitter is GABA?

A

Inhibotry amino acid neurotransmitter

42
Q

What are the 2 types of receptors that use the inhibotry amino acid neurotransmitter GABA?

A

Ionotropic
Metabotropic

43
Q

What ligand gated ion channels are important at synapses that uses glutamate (excitatory synapse)?

A

AMPA
NDMA

44
Q

What is the role of AMPA receptors at glutamatergic synapses?

A

Mediate fast initial depolarisation

45
Q

What ion are NMDA receptors at glutamateric synapses permeable to?

A

Ca2+ (Glutamte needs to bind to NMDA and cell needs to be depolarised for Ca2+ to flow)

46
Q

What is the co-agonist for NMDA except for glutamte?

A

Glycine

47
Q

What brain function does glutamte receptors. Have?

A

Learning and memory

48
Q

How are glutamate receptors improtant in learning and memory?

A

Activation of NMDA receptors can up regulate AMPA receptors

Strong high frequency stimulation causes long term potentiation
Ca2+ entry through NMDA receptors important for induction of Long Term potentiation

49
Q

What causes excitotoxicity?

A

Too much Ca2+ entry through NMDA receptors
Too much glutamate

50
Q

What is the main inhibitory amino acid in the brain ?

A

GABA

51
Q

Where does glycine act mostly as an inhbitory neurotransmitter?

A

Brainstem and spinal cord

52
Q

What is the method that GABA and Glycine acts as an inhibitory neurotransmitter?

A

GABAa and glycine receptors have integral Cl- channels

Opening Cl- channels leads to Cl- influx into neurone leading to hyperpolarisation causing an inhbitory post-synaptic potential which decreases the firing of action potentials

53
Q

What 2 drug types increase the activity of GABA receptors in the brain?

A

Barbiturates
Benzodiazepines

54
Q

What effects do barbiturates and benzodiazepines have by enhancing the response of GABA receptors to the inhbitory neurotransmitter GABA?

A

Anxiolytic and sedative

But barbiturates not used for this anymore

55
Q

Why are barbiturates not used for anxiolytics and sedatives anymore?

What is it sometimes used for?

A

Risk of fatal OD, dependance and tolerance

Antiepileptic

56
Q

What is benzodiazepines used to treat?

A

Anxiety
Insomnia
Epilepsy

57
Q

What type of neurones use glycine as an inhibitor neurotransmitter?

A

Inhbitory interneuroens (neurones between neurones)

58
Q

What is the function of glycine released in the spinal cord during REM sleep?

A

Inhibits lower motor neurones (LMN) causing paralysis

59
Q

What are biogenic amine neurotransmitters typically used for?

A

Modulators role in specific brain pathways

60
Q

What are the main biogenic amine neurotransmitters?

A

ACh
Noradrenaline
Dopamine
5-HT (serotonin)
Histamine

61
Q

Where is ACh used as a neurotransmitter?

A

Neuromuscular junctions
Ganglion synapse in autonomic nervous system
Postganglionic parasympathetic
Sympathetic cholinergic fibres like to sweat glands

Nicotine and Muscarinic receptors in the brain
(Mainly excitatory)
They are often on presynaptic terminals to enhance the release of other transmitters

62
Q

What neurotransmitter does Ach aid in the release of in the brain?

A

Dopamine

63
Q

What causes addiction with smoking?

A

Activation of nicotinic receptors leads to release of dopamine (a reward substance)

64
Q

Where do cholinergic neurones originate from in the CNS?

A

Basal forebrain and brainstem

65
Q

Where do cholinergic neurones give projections to?

A

Parts of cortex and hippocampus

66
Q

What is an example of an area of the brain containing local cholinergic interneurones?

A

Corpus striatum

67
Q

What are the key pathways produced by the basal forebrain nuclei projecting to cortical areas?

A

Arousal
Learning and memory
Motor control

68
Q

How may anticholinergic drugs affect the brain and why?

A

Drowsiness
Pathway for arousal is ACh mediated

69
Q

What causes Alzheimer’s disease?

A

The degeneration of cholinergic neurones in the nucelus basalis

70
Q

What type of drugs are given to alleviate symptoms of Alzheimer’s disease?

A

Cholinesterase inhbitors

71
Q

What 2 main pathways in the brain are involved in mood, arousal and reward?

A

Mesocortical pathway
Mesolimbic pathway

72
Q

What is the pathway involved in motor control?

A

Nigrostriatal pathway

73
Q

What is the nigrostriatal pathway?

A

Pathway from substantia nigra to the striatum involved in motor control

74
Q

What causes Parkinson’s disease?

A

Degeneration of the nigrostriatal pathway
Or
Associated with loss of dopaminergic neurones

75
Q

How is Parkinson’s treated?
How does this work?

A

Levodopa
Converted to dopamine by DOPA decarboxylase

76
Q

What causes schizophrenia?

A

To much dopamine being released

E.g amphetamine releases dopamine and noradrenaline this produces schizophrenic like behaviour

77
Q

How do antipsychotic drugs normally work?

How is schizophrenia treated?

A

Antagonists to dopamine receptors

D2 receptor antagonist

78
Q

What is the mesolimbic pathway?

What neurotransmitter does it use?

A

From midbrain to limbic system (hippocampus, amygdala)

Important in mood arousal and reward

Dopamine

79
Q

What disease does over activity of the mesolimbic system contribute to?

A

Schizophrenia

80
Q

What is the neocortical pathway?

A

Dopamine pathway from midbrain to cerebral cortex

81
Q

What drug is given for Parkinson’s disease?

A

L-DOPA with Carbidopa

82
Q

How does L-DOPA and Carbidopa help treat Parkinson’s?

A

L-DOPA converted to dopamine in brain by enzyme aromatic amino acid decarboxylase

L_DOPA readily crosses BBB
L-DOPA can problematically be converted to dopamine in the periphery’s
Carbidopa stops this (inhibits AADC in the periphery)
Carbidopa cant cross the blood brain barrier

83
Q

What are the negative side effects oof high dopamine in the periphery?

A

Heart GI and urinary side effects

84
Q

What type of receptors does noradrenaline work on/

A

GPCRs

85
Q

Where are the cell bodies for noradrenaline found ?

A

Brainstem like in the locus coeruleus

86
Q

What role does noradrenaline serve in the brain?

A

Behavioural arousal

87
Q

How do locus coeruleus neurones act during sleep then waking?

A

These noradrenaline mediated neurones are inactive in sleep and activity increase when waking

88
Q

What affect do amphetamines have on the brain?

A

Increase levels of noradrenaline and wakefulness (locus. Coeruleus)

89
Q

What condition is associated with a deficieny of noradrenaline?

A

Depression

90
Q

How is depression treated?

A

Drugs that increase noradrenaline in the brain

91
Q

How are serotonergic pathways distributed through the CNS?

A

Similar distribution to noradrenergic neurones

92
Q

What is the function of serotonin (sertonergic) pathways in the CNS?

A

Sleep and wakefulness
Mood

93
Q

Where do 5-HT/serotonin neurones originate from?

A

Raphe nuclei of brainstem

94
Q

What can low levels of serotonin cause?

A

Depression

95
Q

What drugs can be used to help treat depression and anxiety when serotonin is deficient?

A

Selective serotonin re uptake inhibitors

96
Q

What is an example of an SSRI?

A

Fluoxetine (also called Prozac)

97
Q

What are some peptide neurotransmitters involved in pain transmission?

A

Dynorphin
Encephalitis

98
Q

What is an excitroary post synaptic potential?

A

The depolarisation in the post synaptic membrane following a ligand binding to an ioniotropic receptor leading to an influx of cations causing depolarisation

99
Q

How does more neurotransmitter in synapse affect the excitatory post. Synaptic potential?

A

Inc magnitude of excitiory post synaptic potential
Increased frequcney of action potentials

Y2 - CNS (21 decks)

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