2.1 Roles of Neurones and Glia Flashcards
What are the roles of Glial cells
Glia support, nourish and insulate neurones and remove ‘waste’
What are the types of Glial cells (neuroglia)?
- Astrocytes (several different types) - most abundant type of glial cell
- Oligodendrocytes - insulators
- Microglia - Immune responses
What are the roles of astrocytes?
- Structual support
- Help form the BBB
- Glucose-lactate shuttle - help provide nutrition for neurones
- Remove neurotransmitters (uptake) - control concentration of neurotransmitters (especially important for glutamate - toxic)
- Maintain ionic environment (K+ buffering)
How do astrocytes provide energy for neurones?
Neurones do not store or produce glycogen.
Astrocytes produce lactate which can be transferred to neurones by the ‘glucose-lactate shuttle’. This supplements the neurons for supply of glucose.
There is a transastrocyte path and a direct path for the transport of glucose.
How do astrocytes keep extracellular concentrations of neurotransmitters low?
Astrocytes help to remove neurotransmitters through use of transporter. By doing this they help to kepe the extracellular concentrations low. Otherwise excess neurotransmitter can have toxic effects (e.g. Glutamate = excess Ca2+ released)
How do astrocytes help to buffer K+ in the brain ECF?
High levels of neuronal activity can lead to a rise in K+ in the ECF. Astrocytes take up K+ to prevent this.
If K+ wasnt buffered, this could cause a hyperexcitable environment in the brain.
Astrocytes are permeable to Cl- ions too, causing a negative membrane potential which promotes K+ uptake.
What is the role of Oligodendrocytes?
Oligodendrocytes myelinate axons in the CNS (Schwann cells act do the PNS)
What is the role of Microglia?
Microglia (essentially macrophages of the brain) are immunocompetent cells, they are the brains main defence system.
They recognise foreign material and become activated then phagocytose the debris and foreign material.
Outline the role, structure and permeability of the blood brain barrier.
The BBB limits diffusion from the blood to the brain extracellular fluid - maintaining the correct environment for neurons.
Brain capillaries have tight junctions between endothelial cells, BM surrounding capillaries, and the end feet of astrocyte processes. (endothelial cells form the BBB, astrocyte foot processes associated with capillaries)
Glucose, AA, K+ transported across BBB - transporters allow the concentrations to be controlled.
Explain how the CNS is immune privileged (specialised)
Too much inflammation in the brain can lead to herniation therefore we cant different immune responses within the brain that minimise inflammation.
- Microglia act as APCs
- T-cells can enter the CNS but the CNS inhibits pro-inflammatory T cell responses.
Neurones communicate via synapses - what are the 3 different types of synapses
- Fast-excitatory
- Fast-inhibitory
- Modulatory responses
What are the 4 main sections of the neuronal structure?
- Cell soma (body)
- Dendrites
- Axon
- Terminal
How does neurotransmitter release occur?
- Depolarisation of the presynaptic terminal opens VGCC’s leading to calcium influx.
- Calcium binds to synaptotagmin
- Vesicles are brought closer to the membrane
- Snare complex forms fusion pore.
- Transmitter released through the pore.
Neurotransmitter then diffuses across the synaptic cleft and binds to receptors on postsynaptic membrane.
What does the postsynaptic response depend on?
Postsynaptic response depends on the:
- Nature of the transmitter
- Nature of the receptor (LGIC and GPCR)
What are the 3 chemical classes of neurotransmitter
- Amino acids (excitatory = glutamate; inhibitory = glycine and GABA)
- Biogenic amines (acetylcholine, noradrenaline, dopamine, serotonin, histamine)
- Peptides (dynorphin, enkephalins, substance P, somatostatin, CCK, neuropeptide Y)
What are the 2 different Glutamate receptors
- Ionotropic - activation causes depolarisation and an increase in excitability
- AMPA = Na+/K+
- Kainate = Na+/K+
- NMDA = Na+/K+/Ca2+ - Metabotropic - mGluR1-7, GPCR
- changes in IP3 and Ca2+ mobilisation (Gq)
OR
- changes adenylate cyclase and decreased cAMP levels (Gi)
Explain how fast-excitatory neurotransmitters work
Excitatory neurotransmitters cause depolarisation of postsynaptic cleft by acting on ligand gated ion channels. They cause an excitatory post-synaptic potential, depolarisation causes more action potentials.
Glutamatergic synapses
- AMPA and NMDA receptors
- AMPA = inital fast depolarisation
- NMDA = permeable to Ca2+ (NMDA receptors requires glutamate binding and cell to be depolarised already; glycine can act as a co-agonist)
Outline the actions of glutamate on NMDA receptors (including the role of glutamate receptors and the consequences of NMDA receptor activation - esp synaptic plasticity)
Glutamate receptors role in learning and memory
Activation of NMDA (and mGluRs) can upregulate AMPA receptors
Strong, high frequency stimulation causes long-term potentiation (LTP)
Ca2+ entry through NMDA receptors is important for induction of LTP (useful in long term memory)
Too much Ca2+ through NMDA receptors = excitotoxicity (too much neuronal excitation, can be caused by excess glutamate)
Outline the roles of Barbituates and Benzodiazepines
GABA = main inhibitory NT in brain
- Barbituates and Benzodiazepines are GABA potentiators and bind to GABAa receptors and enhance it’s inhibitory response.
- Both have sedative and anxiolytic effects (treat anxiety and epilepsy)
- Both can cause dependence
- Barbituates especially have a risk of fatal overdose
Outline how GABAa receptors and Glycine act
Glycine acts as inhibitory NT mostly in the brainstem and spinal cord.
GABAa receptors and glycine have integral Cl- channels. Opening of the chloride channel causes hyperpolarisation = ‘inhibitory post-synaptic potential’ which decreases action potential firing
What is the action of GABAb receptors
GABAb receptors are GCPRs which have a modulatory role.
GPCR therefore are metabotropic receptors which have modulatory roles
Outline how reflexes work with neurotransmitters and synpases (use the knee reflex for an example)
There is an excitatory and an inhibitory synapse
Quadriceps contract therefore are excitatory (use of glutamate)
Hamstrings relax therefore are inhibitory (use of glycine)
This occurs in the spinal cord.
Give some examples of Biogenic amines and acetylcholine and briefly how they act
Acetylcholine, dopamine, noradrenaline, serotonin (5-HT)
Mostly act as NEUROMODULATORS - confined to specific pathways
Explain how acetylcholine acts as a neurotransmitter and where it works.
Acts at neuromuscular junction, ganglion synapse in ANS, postganglionic parasympathetics
ACh is also a central NT, acting at nicotinic and muscarinic receptors in the brain - mainly excitatory effects.
- ACh receptors on presynaptic terminals enhance the release of other NT’s
