Flashcards in 3. The Role Of Neurones And Glia Deck (79):
What is the basic role of neurones?
To communicate with each other and sense changes
What is the basic role of glia?
Support, nourish, and insulate neurones, and remove waste
What are the 3 types of glial cells?
Which type of glia are the most abundant?
What is the role of astrocytes?
Which type of glial cells are responsible for insulation?
What do microglia do?
Immune response within the CNS
Which cells help form the blood-brain barrier?
How do astrocytes “support” the CNS?
How are neurones supplied with glucose?
Glucose-lactate shuttle in astrocytes
Why do astrocytes need to provide the lactate to the CNS?
Neurones do not store or produce glycogen themselves, so the glucose that crosses the BBB is supplemented by lactate from astrocytes
When are astrocytes most important wrt energy supply?
When blood glucose is low
Describe the mechanism by which astrocytes supplement neuronal glucose supplies.
Glucose crosses BBB via GLUT 1 transporter into the astrocyte, where it is stored as glycogen. This can be converted into pyruvate then lactate when needed. Lactate is transported with H+ via MCT1&2 transporters where it is converted to pyruvate for ATP.
Why is it important for astrocytes to remove neurotransmitter?
Without reuptake/control by astrocytes, build up can cause toxicity.
Also allows neurones to reset and refire
Give an example of a neurotransmitter that can become toxic if it builds up.
What ion is chiefly buffered by astrocytes in the brain?
What can cause excess K+ in the brain ECF?
Neuronal activity increase causes release of K+ into ecf
How many pathways do astrocytes use to mop up excess K+?
By what 3 mechanisms do astrocytes mop up K+?
-K+ and Cl- move into glial cells via channels together due to very negative MP of glial cells
What do oligodendrocytes myelinate?
How many axons does one oligodendrocyte myelinate?
When are microglia activated?
When they recognise foreign material
How do microglia remove debris/foreign material?
What is the main function of the BBB?
Limit diffusion of substances from blood to brain to maintain the correct environment for neurones
Describe the structure of the BBB.
Capillaries in the brain have tight junctions between the endothelial cells of the vessels, the BM surrounding the capillary, and the end of the feet of the astrocyte processes. Microglia also surround these junctions.
What are some of the important substances that the BBB regulates (from the very long list)?
What is special about the immune system of the CNS?
It does not undergo rapid rejection of allografts, unlike the rest of the body as too much inflammation will be harmful as rigid skull will not tolerate volume expansion.
How do microglia act to trigger an immune response in the CNS if necessary?
Act as antigen presenting cells so T cells can enter the CNS
What kinds of signals can occur at the synapse?
How does neurotransmitter release occur?
-Opens VG Ca2+ channels -> Ca2+ influx
-Vesicles of neurotransmitter respond to increase in Ca2+
-Vesicles fuse with end plate and release transmitter
What does the post-synaptic response to a neurotransmitter depend on?
Nature of the transmitter
Nature of the receptor
What 3 broad categories can neurotransmitters be divided into?
What amino acids can commonly act as CNS neurotransmitters?
What are some of the biogenic amines that act as CNS neurotransmitters?
What are some of the peptides that act as CNS neurotransmitters?
Which amino acid is the most common neurotransmitter?
Is glutamate an excitatory or inhibitory neurotransmitter?
Which amino acid neurotransmitters are inhibitory?
What % of all CNS synapses are glutamatergic?
70%, evenly distributed throughout CNS
What are the 3 types of ionotropic glutamate receptors?
AMPA. Kainate, and NMDA receptors
What is EPSP?
Excitatory post-synaptic potential i.e. depolarisation causes more APs to be generated
What receptor do glutamatergic synapse have?
AMPA and NMDA
What do these 2 types of receptor do within the glutamatergic synapse?
AMPA mediate initial fast depolarisation, and NMDA are Ca2+ permeable so mediate long term potentiation of APs.
Which neurotransmitter receptors have a very important role in learning and memory?
How are glutamate receptors involved in learning and memory?
NMDA receptors activated can upregulate AMPA receptors. If stimulation is strong, high, and regular, there is long term potentiation.
With glutamate receptors, what can cause excitotoxicity?
Too much Ca2+ or too much glutamate
What is the main inhibitory a.a. in the CNS?
What kind of ion channels are GABA and glyceine receptors?
What does a Cl- influx cause?
IPSP - inhibitory post synaptic potential
How can we utilise GABA in a clinical setting?
With GABA agonists for anxiolytic effect and sedative action
Name the GABA agonists we use.
Barbiturates and Benzodiazepines
Where is glyceine present most?
Brainstem and spinal cord (released by inhibitory neurones e.g. in knee jerk to inhibit knee flexor contracting)
Where are biogenic amines used?
In specific pathways in the CNS
Where does ACh act?
NM junction, ganglion synapse in ANS, postganglionic in PSNS, and centrally also.
What receptors does ACh act on?
Nicotinic and Muscarinic receptors
Is ACh ususally excitatory or inhibitory?
Where in the brain do the main cholinergic pathways originate from?
Basal forebrain and brainstem
Where do the cholinergic pathways spread to?
Many parts of the cortex and hippocampus
Where are there local cholinergic neurones?
In a few places e.g. the corpus striatum. These are interneurones.
What are the cholinergic pathways involved in?
Arousal, learning, memory, and motor control.
What is degeneration of cholinergic pathways associated with?
What can we use to alleviate the symptoms of Alzheimers disease?
What is the nigrostriatal pathway involved in?
Which pathways are involed in mood, arousal, and reward?
Mesocortical and mesolimbic
What are the main conditions associated with dopamine dysfunction?
Parkinson's disease and Schizophrenia
Tell me about Parkinson's disease.
Associated with loss of dopaminergic neurones in the substantia nigra, which means corpus striatum is less stimulated.
What can we treat the symptoms of Parkinson's with?
Levodopa which is converted to dopamine
What converts Levodopa to dopamine?
Tell me about Schizophrenia.
May be due to too much dopamine, therefore treated partially with D2 antagonists.
Which drugs can cause schizophrenic-like behaviour, and how does it work?
Amphetamines - cause dopamine and NA release
What is the problem with giving levodopa?
Not all the dopamine gets to the CNS as much of it is converted in the periphery. Carbidopa should be given alongside levodopa to inhibit AADC converting levodopa to dopamine in the periphery
What is AADC?
Aromatic amino acid decarboxylase
Where does most of the NA in the brain come from?
It is produced by a group of neurones in the locus ceruleus
When is the locus ceruleus inactive?
When does NA release increase?
Behavioural arousal and wakefulness
What do amphetamines do in the brain?
Increase NA and dopamine release
Where is NA released throughout the brain?
Diffuse release throughout the cortex, hypothalamus, amygdulla, and cerebellum.
Where are serotonergic neurones distributed?
Diffusely throughout the cortex, hypothalamus, amygdulla, and cerebellum.