Session 2 The Role Of Neurones And Glia Flashcards by Amber Torkington

difference between the functions (general) of neurones and glia?

How many neurones are there and how many glia (estimate!)?

Neurones = sense changes and communicate with other neurones

Glia = support, nourish and insulate the neurones and also remove waste

Neurones 10[11]
Glia 10[12]

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What are the three types of glial cells (neuroglia)?

What are their main functions?

Astrocytes = most abundant and are supporters
Oligodendrocytes = insulators
Microglia (the smallest!) = immune response

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What are the 5 main roles of astrocytes?

Structural support
Help in providing nutrition for neurones
Remove neurotransmitters (take them up)
- allow concentrations of the neurotransmitters to be controlled
Maintain an ionic environment (by buffering k+)
Help to form the blood brain barrier

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How do astrocytes help to provide energy for neurones?

What is this process called?

Neurones dont store or produce glycogen so astrocytes will produce lactate which can be transferred to the neurones which can be used for energy when neurones are very active

Glucose lactate shuttle
* astrocytic lactate (that was synthesised by glycolysis of glucose) is release to the extra cellular space and taken up by neurones through monocarboxylase transporters

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Why and how do astrocytes help to remove neurotransmitters?

astrocytes have transporters for transmitters (e.g. glutamate) which help to keep the extracellular concentration of these neurotransmitters low

Too much glutamate is toxic = excitotoxity

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What is the importance of astrocytes ability to help buffer k+ in the brain ECF?

High levels of neuronal activity have the potential to lead to a rise in K+ concentration in the brain ECF BUT astrocytes take up the k+ to prevent this

Astrocytes have a very negative resting membrane potential :)

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What is responsible for myelination of axons in;
A) CNS
B) PNS

A) oligodendrocytes (myelin wrapping)

B) schwann cells (layers of myelin sheath)

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What is the role of microglia?

They are immunocompetent cells
They recognise foreign material such as plaques and debris and are activated
They can perform phagocytosis to remove this foreign material

They are the brain’s main defence system!

Resting > Activated > phagocytic
(Thin and spindly) > large blob

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What does the blood brain barrier do?

What do brain capillaries have (as in what are they made up of)?

Limits diffusion of substances from the blood to the brain ECF

Maintains the correct environment for neurones

Brain capillaries have:

tight junctions that are found between the endothelial cells
a basement membrane that surrounds the capillary
end feet of astrocyte processes

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What substances are transported across the BBB?

Glucose
Amino Acids
Potassium

allow the concentration to be controlled

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The CNS is ‘immune privileged’ (immune specialised) what does this entail?

The brain doesn’t rapidly reject allografts (donor)

The skull is very rigid and so cant undergo a lot of volume expansion which would accompany inflammation = harmful

Microglia act as antigen presenting cells allowing T cells to enter the CNS

But the CNS inhibits the initiation of the pro-inflammatory T cell response

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What are the four main structures of a neuron?

Cell soma (the round bit)

Dendrites

Axon (with myelin sheath and nodes of ranvier)

Terminals (lots which synapse on dendrites of other neurons)

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What happens in the presynaptic terminal when depolarisation occurs?

Opening of voltage gated calcium ion channels

Calcium ions will enter the terminal

Vesicles fuse and release neurotransmitter

The neurotransmitter then will diffuse across the synaptic clef and bind to receptors on the post synaptic membrane (normally on dendrite)

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What does the postsynaptic response normally depend on?

The nature of the transmitter

The nature of the receptor

ligand-gated ion channel
G-protein coupled receptors

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What are the three chemical classes of neurotransmitters in the CNS?

Amino Acids
Biogenic amines
Peptides

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Name three neurotransmitters that are in the amino acid class

GABA

Glutamate

Glycine

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Name 5 neurotransmitter’s that are in the biogenic Amines class.

ACh 
Noradrenaline
Dopamine
Serotonin (5-HT) 
Histamine

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Name 6 neurotransmitters that are in the peptides class

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Dynorphin
Enkephalins 
Substance P 
somatostatin 
Cholecystokinin
Neuropeptide Y

What is the main excitatory (amino acids) neurotransmitter in the CNS?

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Glutamate

Over 70% of all CNS synapses are glutamatergic

What are the main inhibitory (amino acid) neurotransmitters?

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GABA

Glycine

What are the two main types of glutamate receptors? Plus subtypes!

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Can be ionotropic or metabotropic

Ionotropic include:

AMPA receptors
Kainate receptors
NMDA receptors

Metabotropic = mGluR1-7

What type of receptors are ionotropic glutamate receptors?

What are they permeable to?

What does their activation cause?

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Ion channels!

AMPA and Kainate receptors are permeable to;
Na+ and K+

NMDA are permeable to Na+, K+ AND Ca2+ !!!

activation causes depolarisation (increased excitability!)

What type of receptors are metabotropic glutamate receptors?

What are they linked to?

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G protein coupled receptors

Linked to either..

Changes in IP3 and Ca2+ mobilisation

Inhibition of adenylate cyclase and decreased cAMP levels

How do excitatory neurotransmitters cause depolarisation of the postsynaptic cell?

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By acting on ligand gated ion channels

excitatory postsynaptic potential (EPSP)

Depolarisation causes more action potentials

Basically bring up potential towards threshold

What is special about NMDA receptors?

As well as being permeable to sodium and potassium ions, they are also permeable to calcium ions NMDA receptors need glutamate to bind AND the cell to be depolarised to allow ion flow through the channel BOTH THINGS!! Glycine can also act as a co-agonist magnesium ions normally block the pores that glutamate need to bind to so they need a depolarisation to push out this magnesium ion which enables the channel to open

What causes long term potentiation and was is important for the induction of long term potentiation? (Once answered) What happens if there is TOO much calcium ion entry through NMDA receptors?

Strong, high frequency stimulation causes long term potentiation Calcium ions try though NMDA receptors is important for induction Activation of NMDA receptors can up-regulate AMPA receptors If there’s too much calcium ion entry through NMDA receptors it will cause excitotoxicity (too much glutamate)

What is the main inhibitory transmitter in the brain?

GABA

What mostly acts as a neurotransmitter in the brainstem and spinal cord?

Glycine

GABAa and glycine receptors have integral Cl- channels. What happens when these open?

Hyperpolarisation! Leads to inhibitory post-synaptic potential (IPSP) Which will DECREASE action potential firing (hence inhibitory)

What do barbiturates and benzodiazepines do in terms of receptors and transmitters? What are these drugs used for?

They bind to GABAa receptors and both enhance the response to GABA Barbiturates - have anxiolytic and sedative actions and are sometimes used as anti-epileptic drugs Benzodiazepines - have sedative and anxiolytic effects - these are used to treat anxiety, insomnia and epilepsy

What do inhibitory interneurones in the spinal cord release?

Glycine! Glycine is in high concentration in the spinal cord and brainstem

Couple of key points about ACh?

* lots of it at the NMJ * it’s a central neurotransmitter - acts at nicotinic AND muscarinic receptors in the brain - mainly excitatory

Where do neurones containing ACh originate from?

Basal forebrain and brainstem There are also local cholineric interneurones in the corpus striatum

Degeneration of cholinergic neurones found WHERE is associated with Alzheimer’s disease? What can you give to alleviate symptoms of Alzheimer’s?

Degeneration of cholinergic neurones in the NUCLEUS BASALIS * give cholinesterase inhibitors to alleviate symptoms As cholinesterase breaks down ACh normally Inhibiting this enzyme will increase the amount of ACh around

What are the cholinergic pathways in the CNS involved with?

Arousal, learning and memory Motor control

Which dopaminergic pathways in the CNS are involved with: A) motor control B) mood, arousal and reward

A) Nigrostriatal pathway B) Mesocortical pathway + Mesolimbic pathway

What are some conditions associated with dopamine dysfunction? Treatment?

1. Parkinson’s disease This is associated with LOSS of dopaminergic neurones - substantia Nigeria input to corpus striatum - can be treated with levodopa which is converted to dopamine by DOPA decarboxylase (AADC) 2. Schizophrenia This may be due to release of TOO MUCH dopamine - antipsychotic drugs are antagonists at dopamine D2 receptors

How do we stop there being too much dopamine in the periphery but enough goes across the BBB to the brain?

Give L-DOPA which can readily cross BBB where it is converted to dopamine by AADC Give Carbidopa which cant cross the BBB but will inhibit the AADC in the periphery, stoping L-DOPA being converted to dopamine here (as it inhibits AADC) but allowing it still to cross the BBB (Ref to lecture if confused)

What type of receptors does noradrenaline act through?

GPCR’s Alpha and beta adrenoceptors Receptors to noradrenaline in the brain are the same as in the periphery

Where do you find the cell bodies of NA containing neurones?

In the brainstem (pons and medulla) There is diffuse release of NA throughout cortex, hypothalamus, amygdala and cerebellum though!

Where does most of the NA in the brain come from? When are these neurones active/inactive?

A group of neurones in the LOCAL CERULEUS * these are inactive during sleep * activity increases during behavioural arousal * amphetamines increases release of NA and dopamine and increases wakefulness

There is a relationship between mood and the state of arousal. What may depression therefore be associated with?

Deficiency of NA

Distribution of Serotonin? Where found in brain? Functions?

Similar distribution to NA Raphe Nuclei! Functions: sleep/wakefulness and mood

What are SSRI’s and what do they do?

Serotonin selective reputable inhibitors Treat depression and anxiety

Session 2 The Role Of Neurones And Glia Flashcards

(44 cards)