L3- Cellular Physiology of the Brain

Question 1

Which cell types are found in the CNS?

Answer 1

1. Neurones

2. Glial cells

Question 2

Name the different classes of glial cells in the CNS?

Answer 2

1. Astrocytes
2. Microglia
3. Oligodendrocytes

Question 3

Describe the functions of astrocytes?

Answer 3

1. Structural support
2. Nutritional support (glucose- lactate shuttle)
3. Neurotransmitter re-uptake
4. Aids formation of blood brain barrier
5. Maintains ionic environment (I.e. Buffers K+)

Question 4

How do astrocytes provide nutritional support to neurones? Describe this mechanism.

Answer 4

Via glucose-lactate shuttle.
Neurones can’t make energy stores.
Astrocytes store glucose as glycogen which can be broken down to lactate and used by neurones

Question 5

Describe the function of oligodendrocytes.

Answer 5

Myelinate axons in CNS

Question 6

Describe the function of microglia.

Answer 6

Main immune cells of CNS, when activated they grow in size and then phagocytose foreign material. APC.

Question 7

Describe the structure of the blood brain barrier.

Answer 7

Formed from capillary endothelial cells, tight junctions and basement membrane.
Astrocyte foot processes play role in activating formation of tight junctions

Question 8

Describe the steps that result in neurotransmitter being released at the nerve terminal.

Answer 8

1. A.p is initiated and propagates down the axon
2. A.p causes depolarisation of nerve terminal
3. VOCC open
4. Calcium enters nerve terminal
5. Calcium binds to synaptotagmin on pre-synaptic membrane
6. Calcium/ synaptotagmin complex attracts neurotransmitter vesicle towards membrane
7. Neurotransmitter vesicle associates with snare complex, forming a fusion pore
8. Neurotransmitter released

Question 9

Name the 3 chemical classes of neurotransmitter in the CNS and give examples for each.

Answer 9

1. Amino acids- glutamate, glycine, GABA
2. Biogenic amines- acetylcholine, noradrenaline, dopamine, serotonin, histamine
3. Peptides- enkephalins, somatostatin, cholecystokinin, substance P

Question 10

Which neurotransmitter is involved in the majority of synapses in the CNS?

Answer 10

Glutamate (excitatory)

Question 11

Which classes of receptors does glutamate act on?

Answer 11

1. Inotropic (integral ion channel)

2. Metabotropic (GPCR)

Question 12

Name 3 glutaminergic ionotropic receptor sub-types and which ions do they transport?

Answer 12

1. AMPA- sodium, potassium
2. NMDA- sodium, potassium, calcium
3. Kainate- sodium, potassium

Question 13

Which 2 things do NMDA receptors require to open?

Answer 13

1. Glutamate
2. Depolarisation of post synaptic neurone (achieved by fast acting AMPA receptors, also present at synapse, opening in response to glutamate allowing an influx of sodium)

Question 14

Explain why high levels of glutamate can be toxic to neurones, what is this called?

Answer 14

Excitotoxicity
High levels of glutamate (e.g. released from damaged neurones during a stroke) causes NMDA receptors to be excessively stimulated meaning a harmful amount of calcium enters the neurone

Question 15

Name 1 action of glutamate in the brain, why is the NMDA receptor essential for this?

Answer 15

Learning/memory
NMDA receptor allows calcium to enter the post synaptic neurone, this creates a strong and high frequency signal which strengthens the synapse> long term potentiation

Question 16

Define long term potentiation?

Answer 16

Long-term potentiation (LTP) is a persistent strengthening of synaptic connections induced by a brief period of high-frequency presynaptic activity and is required for learning and memory

Question 17

Which inhibitory amino acid neurotransmitters are found in the CNS? Where do they primarily act?

Answer 17

GABA- brain

Glycine- brainstem, spinal cord

Question 18

Define the mechanism of GABA(a) and glycine receptors.

Answer 18

Receptors contain an integral chloride channel which allows chloride to enter post synaptic neurone when activated by GABA/glycine causing hyperpolarisation (inhibitory)

Question 19

Which drugs enhance the inhibitory effects of GABA? What are they used for?

Answer 19

Barbituates- anxiolytic, sedative, anti- epileptic. Rarely used now because of risk of overdose, dependence and tolerance.
Benzodiazepines- anxiolytic, sedative used to treat anxiety, insomnia and epilepsy

Question 20

Describe 3 acetylcholine pathways in the CNS.

Answer 20

Nucleus basilis> throughout cerebral cortex
Medial septal nucleus> hippocampus
Pedunculopontine nucleus> thalamus

Question 21

Where in brain is often the first site of neurone degeneration in Alzheimers? How is this managed?

Answer 21

Nucleus basalis

Manage with cholinesterase inhibitors

Question 22

Name and describe 3 dopaminergic pathways in the CNS.

Answer 22

1. Nigrostriatal- substantia nigra> striatum
2. Mesocortical- midbrain> cerebral cortex
3. Mesolimbic- midbrain> hippocampus/ amygdala

Question 23

Describe the therapy for PD.

Answer 23

Give L-DOPA, a dopamine precursor (dopamine can’t cross the BBB). L-DOPA is transported across the BBB via large neutral aa transporter, then converted to dopamine via aromatic aa decarboxylase (DOPA decarboxylase).
L-DOPA must be given alongside carbidopa, an AADC inhibitor, to prevent conversion of L-DOPA to dopamine in the periphery as excess dopamine could be harmful. Carbidopa can’t cross BBB.