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[AMS] 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
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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
  • 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 produce lactate which can be transferred to neurones

⇒ Supplements their supply of glucose

⇒ Glucose-lactate shuttle

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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
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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
  • 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

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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
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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
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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

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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 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)
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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, GABA, glycine
  • 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)
  • 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 e.g. AMPA & NMDA receptors
  • Metabotropic – GPCR linked to changes in IP3 and Ca2+ mobilisation / inhibition of AC and decreased cAMP levels
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
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
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
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
  • 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

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
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)
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
38
Q

Noradrenaline also acts as a neurotransmitter in the CNS.

Explain how it acts in the CNS

A
  • Operates through G protein-coupled α- and β-adrenoceptors
  • Receptors to NA in the brain are the same as in the periphery
39
Q

What is the role of noradrenergic pathways in the CNS?

A
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

[AMS] Clinical Neuroscience (21 decks)

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