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SA Clinical Neuroscience > S2) Cellular Physiology of the Brain > Flashcards

S2) Cellular Physiology of the Brain Flashcards

1
Q

The central nervous system is composed of a network of neurones with supporting glia.

Describe their respective roles

A
  • Neurones sense changes and communicate with other neurones (approx. 1011 neurones)
  • Glia support, nourish and insulate neurones and remove ‘waste’ (approx. 1012 glia)
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2
Q

Identify and describe the three different types of glial cells

A
  • Astrocytes – most abundant type of glial cell, supporters
  • Oligodendrocytes – insulators
  • Microglia – immune response in brain
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3
Q

Describe the five different roles of astrocytes

A
  • Structural support
  • Help with nutrition for neurones (glucose-lactate) shuttle
  • Control [neurotransmitters] through uptake/removal → important for glutamate
  • Maintain ionic environment (K+ buffering)
  • Help form blood-brain barrier
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4
Q

In four steps, explain how astrocytes help provide energy for neurones

A

⇒ Neurones do not store/produce glycogen

⇒ Astrocytes store glycogen and can produce lactate which can be transferred to neurones

⇒ Supplements their supply of glucose

⇒ Glucose-lactate shuttle

→ lactate can convert into pyruvate

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5
Q

Explain how astrocytes help to remove neurotransmitters

A
  • Astrocytes have transporters for transmitters such as glutamate
  • This helps to keep the [extracellular] low in order to limit response and reduce toxicity if glutamate levels rise too much
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6
Q

Explain how astrocytes help to buffer K+ in brain ECF

A
  • High levels of neuronal activity could lead to a rise in [K+] in brain ECF as sodium enters the burin and potassium enters the extracellular space
  • Astrocytes have a very negative RMP to facilitate the uptake of K+ to prevent over-excitation of neurones
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7
Q

What do oligodendrocytes do?

A

Oligodendrocytes are responsible for myelinating axons in CNS

they can myeline multiple axons

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8
Q

Describe the structure and function of microglia cells

A
  • Structure: immunocompetent cells
  • Function: once activated, recognise foreign material and remove debris and foreign material by phagocytosis

Brains main defence mechanism

these cells can sweep and engulf foreign material

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9
Q

What is the purpose 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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10
Q

Describe the features of capillaries in the blood brain barrier

A
  • Tight junctions between endothelial cells
  • Basement membrane surrounding capillary
  • End feet of astrocyte processes

(astrocytes contain receptors to neurotransmitters) → not relevant to this

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11
Q

Which substances can pass freely across the BBB?

A

Substances such as glucose, amino acids and potassium are transported across BBB

oxygens, water, co2 can also freely move across endothelial cells

should limit amount of potassium and amino acids passing over

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12
Q

Describe the typical neuronal structure

A

Four main sections:

  • Cell soma
  • Dendrites
  • Axon
  • Terminals
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13
Q

In five steps, describe the processes occurring in neurotransmission across a synapse

A

⇒ Depolarisation in the terminal

⇒ Voltage-gated Ca2+ channels open

⇒ Ca2+ enter the terminal

⇒ Vesicles fuse with pre synaptic membrane and release transmitter

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

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14
Q

Which factors determine the postsynaptic response?

A
  • Nature of transmitter
  • Nature of receptor (KLING)/ ligand gated ion channel or G protein - coupled receptors
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15
Q

Identify the three chemical classes of neurotransmitters and provide some examples for each

A
  • Amino acids e.g. glutamate (excitatory), GABA, glycine (both inhibitory)
  • Biogenic amines e.g. acetylcholine, noradrenaline, dopamine, serotonin
  • Peptides e.g. substance P, somatostatin, neuropeptide Y
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16
Q

What are the two types of amino acid neurotransmitters?

A
  • Excitatory amino acids – mainly glutamate (over 70% of all CNS synapses are glutamatergic both excitatory and inhibitory)
  • Inhibitory amino acids – GABA, Glycine
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17
Q

Identify and describe the two types of glutamate receptors

A
  • Ionotropic – ion channel is permeable to Na+ and K+, activation causes depolarisation (sodium moves in) increasing excitability e.g. AMPA & NMDA (permeable to ca) receptors
  • Metabotropic – GPCR linked to changes in IP3 and Ca2+ mobilisation / inhibition of Adenylate Cyclase and decreased cAMP levels
    eg. mGluR1-7
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18
Q

Explain how the fast excitatory response occurs

A
  • Excitatory neurotransmitters cause depolarisation of the postsynaptic cell by acting on ligand-gated ion channels (EPSP)
  • Depolarisation causes more action potentials
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19
Q

Glutamatergic synapses have both AMPA and NMDA receptors.

How do these receptors differ?

A
  • AMPA receptors mediate the initial fast depolarisation
  • NMDA receptors are permeable to Ca2+ and need glutamate binding and cell depolarisation to allow ion flow through the channel

glycine acts as a co agonist

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20
Q

Explain how glutamate receptors have an important role in learning and memory

A
  • Activation of NMDA receptors can up-regulate AMPA receptors
  • Strong, high frequency stimulation causes long term potentiation (LTP)
  • Ca2+ entry through NMDA receptors important for induction of LTP (synapse becomes longer)
21
Q

What happens when too much Ca2+ enters through NMDA receptors?

A
  • Too much Ca2+ entry through NMDA receptors causes excitotoxicity
  • Too much glutamate – excitotoxicity
22
Q

Where do the different inhibitory amino acid neurotransmitters act on the CNS?

A
  • GABA is the main inhibitory transmitter in the brain
  • Glycine acts as an inhibitory neurotransmitter mostly in the brainstem and spinal cord
23
Q

Explain the mechanism of action for GABA and Glycine

A
  • GABAA and glycine receptors have integral Cl- channels
  • Opening the Cl- channel causes hyperpolarisation as cl move inside the cell
  • The inhibitory post-synaptic potential (IPSP) leads to decreased action potential firing
24
Q

What do barbiturates and benzodiazepines do?

A
  • Barbiturates and benzodiazepines bind to GABAA receptors
  • Both enhance the response to GABA
25
Q

Describe the effects and use of barbiturates

A
  • Effects: anxiolytic and sedative actions (risk of fatal overdose also dependence and tolerance)
  • Use: sometimes used as anti-epileptic drugs
26
Q

Describe the effects and use of benzodiazepines

A
  • Effects: sedative and anxiolytic actions
  • Use: treats anxiety, insomnia and epilepsy
27
Q

Glycine is present in high concentration in the spinal cord and brainstem.

Explain how it is released

A

Inhibitory interneurones in the spinal cord release glycine

found in the stretch reflex

28
Q

How do biogenic amines act?

A

Biogenic amines mostly act as neuromodulators and are confined to specific pathways

29
Q

ACh is also a central neurotransmitter.

Explain how it acts in the CNS

A
  • ACh acts at both nicotinic and muscarinic receptors in the brain
  • It is mainly excitatory and receptors are often present on presynaptic terminals to enhance the release of other transmitters
30
Q

Describe the course of cholinergic pathways in the CNS

A
  • Neurones originate in basal forebrain and brainstem and give diffuse projections to many parts of cortex and hippocampus
  • There are also local cholinergic interneurones e.g. in corpus striatum
31
Q

What is the role of cholinergic pathways in the CNS?

A

Cholinergic pathways are involved in arousal, learning & memory, motor control

32
Q

Describe the relationship of cholinergic pathways in the CNS with Alzheimer’s disease and the significance of this

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
33
Q

What is the role of dopaminergic pathways in the CNS?

A

mesocortiyal is also involved in arousal

34
Q

Identify two conditions associated with dopamine dysfunction

A
  • Parkinson’s disease
  • Schizophrenia
35
Q

Describe the cause and treatment of Parkinson’s disease

A
  • Cause: associated with loss of dopaminergic neurones – substantia nigra input to corpus striatum
  • Treatment: levodopa – converted to dopamine by DOPA decarboxylase (AADC) and can cross the blood brain barrier
36
Q

Describe the cause and treatment of schizophrenia

A
  • Cause: may be due to release of too much dopamine
  • Treatment: antipsychotic drugs are antagonists at dopamine D2 receptors
37
Q

Illustrate the use of dopamine therapy at the BBB in the treatment of Parkinson’s disease

A

dopamine will enter the periphery however, Parkinson’s only effects the brain. Dopamine will travel to periphery. Carbidopa only inhibits AADC in periphery as it can’t block blood brain barrier so dopamine only enters the brain

38
Q

Noradrenaline also acts as a neurotransmitter in the CNS.

Explain how it acts in the CNS

A
  • transmitter at post ganglionic in ANS and CNS
  • Operates through G protein-coupled α- and β-adrenoceptors
  • Receptors to NorAdrenaline in the brain are the same as in the periphery
39
Q

What is the role of noradrenergic pathways in the CNS?

A

noradrenaline only comes from a small group of neurones in the locus coeruleus

  • LC neurones are inactive during sleep
  • activity increases during behavioural arousal
  • amphetamines increase release of noradrenaline and dopamine and increase wakefulness
40
Q

Describe the course and role of seratonergic pathways in the CNS

A
  • Course: similar distribution to noradrenergic neurones
  • Function: sleep/wakefulness, mood
41
Q

Where is the majority of noradrenaline in the brain found?

A

Most NA in the brain comes from a group of neurones in the locus coeruleus

42
Q

Describe the relationship between noradrenaline and behavioural arousal

A
  • LC neurones inactive during sleep
  • Activity increases during behavioural arousal
  • Amphetamines increases release of NA and dopamine → increase wakefulness
  • Depression may be associated with a deficiency of NA
43
Q

what does immune privileged mean?

A
  • it is a specialisation
  • It does not undergo rapid rejection of foreign material
  • Brain sits in a rigid skull so too much inflammation would harm the brain so can’t have a quick response
44
Q

what role do microglia cells have in protecting the brain?

A
  • antigen presenting cells
45
Q

what role do GABAB G protein coupled receptors have?

A

modulatory role

46
Q

describe what happens in the stretch reflex when you hit the patella tendon

A
  1. stretch of quad muscles
  2. detected by muscle spindle
  3. send info across excitatory neurone up spinal cord
  4. releases glutamate
  5. this activates a motor neurone to release Ach
  6. then the quad muscle contracts
  7. BUT
  8. inhibitory neurone inhibits motor neurone to the antagonistic muscles
  9. so hamstring muscles relax
47
Q

what might depression be a deficiency of

A

NA

48
Q

serotonergic pathways in the CNS

A

similar distribution to noradrenergic neurones, diffuse to the cerebellum and the cortex

functions:

→ sleep/wakefulness

→mood

49
Q

SSRIs

A

→ serotonin selective reuptake inhibitors so there is more serotonin around

→ can treat depression and anxiety disorders

SA Clinical Neuroscience (23 decks)

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