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Semester 4 - Clinical Neuroscience > 3. Cellular physiology of the brain > Flashcards

3. Cellular physiology of the brain Flashcards

1
Q

What are the Components of the central nervous system?

A

Network of neurones with supporting glia

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2
Q

function of neurones

A

• Neurones sense changes and communicate with other neurones

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3
Q

function of glial cells

A

Glia support, nourish and insulate neurones and remove ‘waste’

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4
Q

What are the different types of glial cells?

A

Astrocytes, microglia, oligodendrocytes

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5
Q

What are the functions of astrocytes? (5)

A
  • structural support
  • provide nutrition for neurones
  • remove neurotransmitters (uptake)
  • maintain ionic environment (K+ buffering)
  • help to form blood brain barrier
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6
Q

Do neurones have stores of glycogen?

A

No, do not store or produce glycogen

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7
Q

How do astrocytes provide energy for neurones?

A
  • have glycogen store which is converted to pyruvate and then lactate
  • produce lactate which can be transferred to neurones
    • produce lactate which can be transferred to neurones
  • supplements their supply of glucose
  • lactate can be converted to pyruvate in neurone to produce ATP
  • used when glucose supply reduced
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8
Q

What is the mechanism by which astrocytes provide lactate to neruones?

A

Glucose lactate shuttle

- Monocarboxylate transporters used (MCT1 and MCT2)

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9
Q

Why is uptake of neurotransmitter important by astrocytes, uptake of which one is particularly important?

A
  • toxic to neurones (excito-toxicity)
  • allow response to occur again
    Glutamate important - main excitatory neurotransmitter in the brain
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10
Q

how do Astrocytes help to remove neurotransmitters?

A

Re-uptake
– Astrocytes have transporters for transmitters such as glutamate
– Helps to keep the extracellular concentration low

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11
Q

Why is potassium buffering important?

A
  • High levels of neuronal activity could lead to a rise in [K+] in brain ECF
  • Raised [K+] in the ECF causes depolarisation of neurones and therefore inapproapriate activation of the neurones?
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12
Q

How do astrocytes help buffer K+?

A
  • astrocytes have a relatively more negative resting membrane potential
  • so have the ability to buffer excess potassium
  • Na+/K+ ATPase, NKCC2, Potassium channels
    (astrocytes are also coupled to each other, effectively buffer K+)
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13
Q

What is the functions of oligodendrocytes?

A

Myelinating axons in CNS

- one can myelinate several axons

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14
Q

What is the functions of microglia?

A
  • immunocompetent cells
  • recognise foreign material - activated
  • phagocytosis to remove debris and foreign material
  • brain’s main defence system
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15
Q

How does the appearance of microglia change?

A
  • look like a star (thin projections from body)
  • projections become thicker when they become activated
  • look like a blob when phagocytic
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16
Q

What is the functions of the blood brain barrier?

A
  • Limits diffusion of substances from the blood to the brain extracellular fluid
  • Maintains the correct environment for neurones
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17
Q

What makes up the blood brain barrier?

A
  • tight junctions between endothelial cells
  • basement membrane surrounding capillary
  • end feet of astrocyte processes
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18
Q

What is immune privilege?

A

Certain sites of the human body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response

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19
Q

Why is the CNS immune privileged?

A

Rigid skull will not tolerate volume expansion
- Too much inflammatory response would be harmful
(specialisation not immune isolation)

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20
Q

Can T cells enter the CNS?

A

Yes - antigen presenting cells present

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

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21
Q

What are the different types of synapses in the CNS?

A
  • fast excitatory neurotransmission
  • fast inhibitory neurotransmission
  • modulatory responses
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22
Q

What are the 4 main structures of neurones?

A
  • cell soma
  • dendrites
  • axon
  • terminals
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23
Q

what is transported across blood brain barrier?

A
  • Substances such as glucose and amino acids and potassium are transported across BBB.
  • This allows the concentration to be controlled
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24
Q

How is neurotransmitter released from the presynaptic terminal?

A
  • Depolarisation in the terminal opens voltage-gated Ca2+ channels. Ca2+ ions enter the terminal
  • Vesicles fuse and release transmitter
  • Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane
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25
Q

What does the response to release of neurotransmitter depend on?

A
  • nature of transmitter
  • nature of receptor
    • Ligand-gated ion channels
    • G-protein-coupled receptors
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26
Q

What are the 3 chemical classes of neurotransmitters? give examples

A
  • Amino acids: glutamate, glycine and GABA
  • Biogenic amines: acetylcholine, noradrenlaine, dopamine, serotonin, histamine
  • Peptides: enkephalins, substance P, somatostain, CCK, Neuropeptide Y
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27
Q

What are the main excitatory and inhibitory neurotransmitters in the CNS?

A

Excitatory: glutamate
Inhibitory: GABA, glycine

28
Q

WHat percent of CNS synpases are glutamatergic?

A

70%

29
Q

What are the ionotropic receptors of glutamate and what are they permeable to?

A
  • AMPA: Na+ and K+
  • Kainate: Na+ and K+
  • NMDA: Na+, K+ and Ca+
    (influx of Na+ into postsynaptic cell)
30
Q

What are the metabotropic receptors of glutamate and what are they linked to?

A

mGluR1 - mGluR7
Linked to either:
• changes in IP3 and Ca2+ mobilisation
• or inhibition of adenylate cyclase and decreased cAMP levels

31
Q

What are fast excitatory responses?

A

Excitatory neurotransmitters cause depolarisation of the postsynaptic cell by acting on ligand-gated ion channels
- excitatory postsynaptic potential (EPSP)
depolarisation causes more action potentials

32
Q

Which receptors mediate the initial fast depolarisation?

A

AMPAreceptors

33
Q

What is different about the NMDA compared to AMPA receptors?

A
  • permeable to calcium

- have magnesium ions blocking the pore preventing flow of ions

34
Q

How is flow of ions through the NDMA receptors achieved?

A

Depolarisation of the post synaptic cell by AMPA receptors causes magnesium to be released from the pore of the NMDA receptors allow ions through.

35
Q

which receptors are present on Glutamatergic synapses

A

• Glutamatergic synapses have both AMPA and NMDA receptors

36
Q

what does NDMA receptors need?

A

NMDA receptors need glutamate to bind and the cell to be depolarised
to allow ion flow through the channel

37
Q

WHat is the effect of glycine on NMDA receptors?

A

Acts as a co-agonist

38
Q

What important role do NMDA receptors have?

A

Important role in learning and memory

39
Q

How are NDMA receptors involved in learning and memory?

A
  • 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
40
Q

what happens if Too much Ca2+ enter through NMDA receptors?

A

– Too much glutamate - excitotoxicity

41
Q

What are the main inhibitory neutransmitters in the brain and spinal cord?

A

Brian: GABA, Spinal cord and brainstem: glycine

42
Q

What type of receptors do GABA and glycine have?

A

Ionotropic, integral chloride ion channels

- inhibitory post synaptic potential

43
Q

what effect does GABA and glycine have on receptors?

A

• Opening the Cl- channel causes hyperpolarisation
– Inhibitory post-synaptic potential (IPSP)
• Decreased action potential firing

44
Q

What are 2 classes of drugs that enhance the response to GABA and what are they used to treat?

A

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
45
Q

Give an example of glycine in the spinal cord?

A

Inhibitory interneurones in the spinal cord release glycine (deep tendon reflexes: inhibition of the antagonistic muscles)

46
Q

describe the deep tendon reflex

A
  • stretch receptors in muscle spindle of quadriceps detect stretch caused by hitting knee.
  • an impulse sent along sensory afferent to dorsal root of spinal cord and into grey matter
  • sensory afferent synapses and releases glutamate with motor efferents which cause quadriceps to contract
  • sensory afferents also synapse with interneuron by releasing glutamate
  • the interneuron releases glycine and synapses with another motor efferent to hamstrings which is inhibitory and causes hamstring relaxation
47
Q

Where are acetylcholine often present in the brain and what do they do?

A

– 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

48
Q

What are the different cholinergic pathways in the brain?

A
  • Nucleus basalis (basal forebrain): projects throughout the cortex
  • substantia nigra to the thalamus
  • corpus striatum (striatal interneurones)
  • Septohippocampal nucleus to hippocampus
49
Q

What are cholinergic pathways in the brain associated with?

A

Arousal, learning & memory, motor control

50
Q

How is acetylcholine associated with alzeheimer’s disease and what can therefore be used to alleviate symptoms?

A

Degeneration of cholinergic neurones in the nucleus basalis is associated with Alzheimer’s disease
• Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease

51
Q

What are the 4 major dopamine pathways in the brain?

A
  • Mesocortical pathway (ventral tegmental area in midbrain to prefrontal cortex)
  • mesolimbic pathway (VTA to hippocampus, amygdala, nucleus accumbens)
  • Nigrostriatal pathway (substantia nigrae to striatum)
  • tubero-hypophyseal pathway
52
Q

What are the general functions of the mesocortical and mesolimbic pathway? (3)

A

involved in mood, arousal and reward

53
Q

What are the general function of the nigrostriatal pathway?

A

Motor control

54
Q

What conditions are associated with dopamine dysfunction?

A

Parkinson’s disease

Schizophrenia

55
Q

What is the relationship between dopamine and Schizophrenia and what is used to treat it?

A

• May be due to release of too much dopamine

  • amphetamine releases dopamine & noradrenaline (schizophrenic behaviour)
  • produces schizophrenic like behaviour
  • antipsychotic drugs are antagonists at dopamine D2 receptors
56
Q

What is the relationship between dopamine and parkinson’s disease?

A
  • associated with loss of dopaminergic neurones

- substantia nigra input to corpus striatum

57
Q

How can parkinson’s associated with dopamine dysfunction be treated?

A

Can be treated with levodopa, crosses the blood brain barrier through LNAA - converted to dopamine by DOPA aromatic amino acid decarboxylase (AADC)

58
Q

What must be given with levodopa in dopamine therapy for parkinsons disease?

A

Carbidopa inhibits AADC in the periphery, preventing rise in dopamine there, but cannot cross the blood brain barrier so cannot inhibit AADC in the brain

59
Q

What are the main noradrenergic pathways in the CNS?

A

From locus ceruleus (from the pons) to cortex, hypothalamus, amygdala, cerebellum

60
Q

When is activity of neurones of the locus ceruleus low/high?

A
  • low activity during sleep
  • high activity during behavioural arousal
  • amphetamines increases release of noradrenaline and dopamine and increase wakefulness
61
Q

what is the action of noradrenalin and where does it act?

A
  • Noradrenaline - transmitter at postganglionic – effector synapse in ANS
  • Also acts as a neurotransmitter in the CNS
  • Operates through G protein-coupled α- and β-adrenoceptors
  • Receptors to noradrenaline in the brain are the same as in the periphery
62
Q

what is the association between noradrenaline and depression?

A

Relationship between mood and state of
arousal
– depression may be associated with a
deficiency of NA

63
Q

What is the major serotonergic pathway in the CNS?

A

Raphe nuclei in the brainstem - wide distribution in the cortex, corpus striatum, thalamus, hypothalamuc, hipoocampus, amygdala, cerebellum

64
Q

What are the functions of serotonin pathways in the CNS?

A
  • Sleep/wakefulness

* Mood

65
Q

What are SSRIs used for?

A

SSRIs (serotonin selective reuptake inhibitors) treatment of depression and anxiety disorders

Semester 4 - Clinical Neuroscience (19 decks)

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