L3- Cellular Physiology of the Brain Flashcards
Which cell types are found in the CNS?
- Neurones
2. Glial cells
Name the different classes of glial cells in the CNS?
- Astrocytes
- Microglia
- Oligodendrocytes
Describe the functions of astrocytes?
- Structural support
- Nutritional support (glucose- lactate shuttle)
- Neurotransmitter re-uptake
- Aids formation of blood brain barrier
- Maintains ionic environment (I.e. Buffers K+)
How do astrocytes provide nutritional support to neurones? Describe this mechanism.
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
Describe the function of oligodendrocytes.
Myelinate axons in CNS
Describe the function of microglia.
Main immune cells of CNS, when activated they grow in size and then phagocytose foreign material. APC.
Describe the structure of the blood brain barrier.
Formed from capillary endothelial cells, tight junctions and basement membrane.
Astrocyte foot processes play role in activating formation of tight junctions
Describe the steps that result in neurotransmitter being released at the nerve terminal.
- A.p is initiated and propagates down the axon
- A.p causes depolarisation of nerve terminal
- VOCC open
- Calcium enters nerve terminal
- Calcium binds to synaptotagmin on pre-synaptic membrane
- Calcium/ synaptotagmin complex attracts neurotransmitter vesicle towards membrane
- Neurotransmitter vesicle associates with snare complex, forming a fusion pore
- Neurotransmitter released
Name the 3 chemical classes of neurotransmitter in the CNS and give examples for each.
- Amino acids- glutamate, glycine, GABA
- Biogenic amines- acetylcholine, noradrenaline, dopamine, serotonin, histamine
- Peptides- enkephalins, somatostatin, cholecystokinin, substance P
Which neurotransmitter is involved in the majority of synapses in the CNS?
Glutamate (excitatory)
Which classes of receptors does glutamate act on?
- Inotropic (integral ion channel)
2. Metabotropic (GPCR)
Name 3 glutaminergic ionotropic receptor sub-types and which ions do they transport?
- AMPA- sodium, potassium
- NMDA- sodium, potassium, calcium
- Kainate- sodium, potassium
Which 2 things do NMDA receptors require to open?
- Glutamate
- 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)
Explain why high levels of glutamate can be toxic to neurones, what is this called?
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
Name 1 action of glutamate in the brain, why is the NMDA receptor essential for this?
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
Define long term potentiation?
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
Which inhibitory amino acid neurotransmitters are found in the CNS? Where do they primarily act?
GABA- brain
Glycine- brainstem, spinal cord
Define the mechanism of GABA(a) and glycine receptors.
Receptors contain an integral chloride channel which allows chloride to enter post synaptic neurone when activated by GABA/glycine causing hyperpolarisation (inhibitory)
Which drugs enhance the inhibitory effects of GABA? What are they used for?
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
Describe 3 acetylcholine pathways in the CNS.
Nucleus basilis> throughout cerebral cortex
Medial septal nucleus> hippocampus
Pedunculopontine nucleus> thalamus
Where in brain is often the first site of neurone degeneration in Alzheimers? How is this managed?
Nucleus basalis
Manage with cholinesterase inhibitors
Name and describe 3 dopaminergic pathways in the CNS.
- Nigrostriatal- substantia nigra> striatum
- Mesocortical- midbrain> cerebral cortex
- Mesolimbic- midbrain> hippocampus/ amygdala
Describe the therapy for PD.
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.
