Session 2 - The Role Of Neurones And Glia Flashcards
What is the purpose of glial cells?
To support, nourish and insulate neurones and remove ‘waste’.
What are the 3 main types of glial cells and what are their overall roles?
Astrocytes (several different types) - supporters
Oligodendrocytes - insulators
Microglia - immune response
Outline the roles of astrocytes.
Structural support
Help to provide nutrition for neurones (glucose-lactate shuttle)
Remove neurotransmitters (controls the concentration of neurotransmitters, which is especially important for glutamate which can be toxic)
Maintain ionic environment (K+ buffering)
Help form the blood brain barrier
Do neurones produce and store glycogen?
No, they rely on astrocytes to store glycogen.
Energy is provided to neurones through what two mechanisms?
Diffusion of glucose from the blood through the interstitial space to the neurones.
Glucose lactate shuttle - transfers lactate from astrocytes to neurones.
Explain the mechanism through which astrocytes can provide energy to neurones.
Astrocytes produce lactate from pyruvate. The lactate then exits the astrocytes through MCT1 channels, diffuses across the interstitial space, and is taken up by by neurones through MCT2 channels. Once inside the neurone, lactate is converted back to pyruvate.
How do astrocytes keep the concentration of neurotransmitters in the synapse low?
They allow re-uptake of neurotransmitters. For instance, astrocytes have transporters for glutamate. This helps keep the extracellular concentration of glutamate low, which is important because glutamate is toxic to neurones.
Why would high levels of neuronal activity lead to a rise in [K+] in brain extracellular fluid?
Lots of neuronal activity means lots of action potentials. During an action potential potassium moves out of the neurone, meaning the concentration of potassium outside the cell rises.
How is the rise in extracellular [K+] during high neuronal activity counteracted?
Astrocytes take up excess K+ to reduce the extracellular concentration.
Why is it important that astrocytes buffer K+ in the brain?
Increased extracellular potassium causes increased depolarisation (it decreases the threshold by increasing the resting membrane potential). This leads to inappropriate action potential firing in neurones which can cause things such as epilepsy.
What is the function of oligodendrocytes?
Oligodendrocytes are responsible for myelination of axons in the CNS. (In the PNS Schwann cells are responsible for myelination).
What is the function of microglia?
Immunocompetent cells. They recognise foreign material, become activated and then phagocytose. They can also present antigens to T cells. They are the brain’s main defence system.
What is the purpose of the blood brain barrier?
It limits diffusion of substance from the blood to the brain extracellular fluid. This maintains the correct environment for neurones.
What are the layers of the blood brain barrier?
Endothelial cells (tight junctions between endothelial cells)
Basement membrane surrounding the capillary
End feet of the astrocytes processes
What factors about the CNS mean that it is ‘immune privileged’?
Microglia can act as antigen presenting cells.
T-cells can enter the CNS.
CNS inhibits the initiation of the pro-inflammatory T cell response.
Does not undergo rapid rejection of allografts.
Why is it important that the CNS is able to inhibit the pro-inflammatory T-cell response?
The rigid skull will not tolerate volume expansion caused by the inflammatory response, would cause a rise in intracranial pressure.
What are the four main sections in a typical neuronal structure?
Cell soma (body)
Dendrites
Axon
Terminals
Outline the process of neurotransmitter release across a synapse.
Depolarisation in the terminal opens voltage-gated Ca2+ channels.
Influx of Ca2+ into the terminal.
Vesicles containing neurotransmitters fuse with the presynaptic membrane.
Neurotransmitter released into the synapse.
Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane.
What are the three chemical classes of neurotransmitter? Give examples of each.
Amino acids - e.g. glutamate, GABA, glycine
Biogenic amines - e.g. acetylcholine, noradrenaline, dopamine
Peptides - e.g. somatostatin, cholecystokinin, neuropeptide Y
What is the main excitatory amino acid neurotransmitter?
Glutamate (over 70% of all CNS synapses are glutamatergic)
Give two examples of inhibitory amino acid neurotransmitters.
GABA
Glycine
What are the three types of ionotropic glutamate receptors?
AMPA receptors (Na+/K+) Kainate receptors (Na+/K+) NMDA receptors (Na+/K+ and Ca2+)
These are ligand gated ion channels - permeable to Na+, K+ and in some cases Ca2+. Activation through binding of glutamate to these channels causes movement of these ions and therefore depolarisation of the post-synaptic membrane.
What is the main metabotropic glutamate receptor?
mGluR1-7
This is a G-protein coupled receptor. It is linked to either:
- changes in IP3 and Ca2+ mobilisation
- inhibition of adenylyl cyclases and decreased cAMP levels
Outline the role of glutamate receptors in learning and memory.
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 is important for the induction of LTP.
Why does too much glutamate cause excitotoxicity?
Too much glutamate - too much Ca2+ entry through NMDA receptors causing excitotoxicity.
GABA and glycine are inhibitory amino acids. What are their main sites of action?
GABA - brain
Glycine - brainstem and spinal cord
Explain how GABA and glycine receptors are able to inhibit post synaptic potentials.
GABA and glycine receptors have integral Cl- channels.
Opening the Cl- channels causes hyperpolarisation.
This creates an inhibitory post-synaptic potential (IPSP) resulting in decreased action potential firing.
Name two groups of drugs which have anxiolytic and sedative effects. Which group is no longer used?
Barbiturates - no longer used
- risk of fatal overdose, dependence and tolerance
- sometimes used as anti-epileptic drugs
Benzodiazepines
- have sedative and anxiolytic effects
- used to treat anxiety, insomnia and epilepsy
What neurotransmitter do inhibitory interneurones in the spinal cord release?
Glycine
Glutamate is the major excitatory transmitter, GABA and glycine are the main inhibitory neurotransmitters. Other neurotransmitters have what sort of role within the CNS?
Modulatory role. They are involved in specific pathways.
Where is acetylcholine released from?
Neuromuscular junction
Ganglion synapse in the ANS
Post ganglionic parasympathetic neurones
Many pathways in the CNS
Is acetylcholine mainly excitatory or inhibitory?
Excitatory
Acetylcholine acts at what sort of receptors in the brain?
Nicotinic
Muscarinic
Receptors are often present on presynaptic terminals to enhance the release of other transmitters
Describe the location of cholinergic pathways in the CNS.
Neurones originate in basal forebrain and brainstem.
Give diffuse projections to many parts of the cortex and hippocampus.
There are also local cholinergic interneurones e.g. in corpus striatum
Cholinergic pathways in the CNS are involved in what functions?
Arousal
Learning
Memory
Motor control
Degeneration of cholinergic neurones in the nucleus basalis is associated with what disease?
Alzheimer’s disease
Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s.
Which dopaminergic pathway in the CNS is involved in motor control?
Nigrostriatal pathway
Which two dopaminergic pathways in the CNS are involved in mood, arousal and reward?
Mesocortical pathway
Mesolimbic pathway
Name two diseases associated with dopamine dysfunction.
Parkinson’s disease
Schizophrenia
What causes Parkinson’s disease and how can it be treated?
Loss of dopaminergic neurones
Substantia nigra input to corpus striatum
Can be treated with levodopa (converted to dopamine by DOPA decarboxylase(AADC))
What causes schizophrenia?
May be due to the release of too much dopamine:
- amphetamine releases dopamine and noradrenaline
- produces schizophrenic like behaviour
- antipsychotic drugs are antagonists at dopamine D2 receptors
- other neurotransmitters also implicated
Can dopamine cross the blood brain barrier?
No, but L-DOPA can
Where is noradrenaline released?
Post-ganglionic-effector synapse in ANS
Also acts in the CNS
Noradrenaline binds to what receptors?
G protein coupled alpha and beta-adrenoceptors
Describe the location of noradrenergic pathways in the CNS.
Cell bodies of NA containing neurones are located in the brainstem (pons and medulla).
Diffuse release of NA throughout the cortex, hypothalamus, amygdala and cerebellum.
Most noradrenaline in the brain comes from a group of neurones located where?
Locus ceruleus
What is the effect of amphetamines?
Increase the release of noradrenaline and dopamine and increase wakefulness
Depression may be associated with a deficiency of what?
NA
When does locus ceruleus neurone activity increase and decrease?
Activity increases during behavioural arousal.
LC neurones are inactive during sleep.
What are SSRIs?
Serotonin Selective Re-uptake Inhibitors
What are SSRIs used to treat?
Depression and anxiety disorders
What are the functions of serotonin?
Sleep/wakefulness
Mood
