Neurones and Glia Flashcards
What 2 main components make up the CNS and what are the functions of each component?
Neurones - sense changes and communicae with other neurones
Glia - support, nourish and insulate neurones and remove waste
How many neurones/ glia cells are there in the brain?
Neurones ~1011
Glia ~1012 (x10 more then neurones)
What are the 3 types of glial cells?
- Astrocytes
- most abundant
- supporters
- Oligodendrocytes
- insulators
- Microglia
- immune response
What is the role of astrocytes?
- Structural support
- Help provide nutrition for neurones (glucose-lactate shuttle)
- Remove neurotransmitters (uptake)
- Maintain ionic environment (K+ buffering)
- Help form blood brain barrier
Explain the glucose-lactate shuttle of astrocytes
- Neurones do not store or produce glycogen
- Glucose enters astrocytes by GLUT1 transporter
- Astrocytes produce lactate from glycolysis that can be transported into neurones by MCT1 transporter
- In the neurone, Lactate converted to pyruvate which can be used for energy
Why do astrocytes need to re-uptake neurotransmitters?
- Astrocytes have transporters for transmitters e.g glutamate (major excitatory neurotransmitter)
- Helps to keep extracellular concentration low so a second response can occur
- Too much glutamate causes excito-toxicity to neurones as too much Ca2+ is released
Why is it necessary for astrocytes to buffer K+ in the brain ECF?
- High levels of neuronal activity leads to a rise in [K+] in brain ECT
- Too much K+ causes neurones to depolarise → inadvertantly activating neurones
- The resting membrane potential is more negative and can therefore buffer K+ from ECF
What is the role of oligodenrocytes?
Responsible for myelinating multiple axons at once within the CNS
What are microglia?
Immunocompetent ‘macrophages’ of the brain
Recognise foreign material, once activated dendrites get thicker and become phagocytotic
Remove debris and foreign material - brains main defence system against plaques and dead material
What is the function of the the blood brain barrier?
- Limits diffusion of substances from the blood to the brain ECF
- Maintains correct environment for neurones
- Brain capillaries have
- tight junctions between endothelial cells
- basement membrane surround capillary
- end feet of astrocyte processes
Which substances can be transported across the blood brain barrier?
- Glucose - transported
- Amino acids- transported
- K+ - transported
- Lipid soluble move freely e.g CO2 and O2
- Ions and small molecules can’t move across due to very tight junctions allowing for tight junction
Explain what is meant by ‘The CNS is immune priveleged’
- The brain does not undergo rapid rejection of allografts
- Rigid skull will not tolerate volume expansion- too much inflammatory response would be harmful
- Microglia can act as APCs
- T Cells can enter the CNS but the CNS inhibits the pro-inflammatory T cell response
Identify the dendrites, soma, axon, terminals, internodes and myelin sheath
How is neurotransmitter released at the synpase?
- Action potential arrives at the pre-synaptic terminal
- Depolarisation of the terminal opens VGCC
- Ca2+ ions enter the terminal
- Vesicles fuse with pre synaptic membrane and transmiter is released
- Transmitter diffuses across the cleft and binds to receptors post-synaptically
What does the postsynaptic response depend on?
- nature of transmitter
- nature of receptor
- ligand gated ion channel
- GPCR
What are the 3 main chemical classes of neurotransmitter?
What are the main amino acid neurotransmitters?
Excitatory - mainly Glutamate major excitatory neurotransmitter (70% of all CNS synapses are glutamatergic)
Inhibitory - GABA and Glycine
What are the main types of Glutamate receptors?
IONOTROPIC - integral ion channels
- AMPA receptors (Na+/K+)
- Kainate receptors (Na+/K+)
- NMDA receptors (Na+/K+ and Ca2+)
Activation causes depolarisation increasing excitability → AMPA and NMDA mainly at synapses causing fast neurotransmission
METABOTROPIC - GPCR
- mGluR1-7
- Linked to either IP3 and Ca2+ mobilisation
- or inhibition of AC and decreased cAMP
Glutamergic synspases have both AMPA and NMDA receptors. Explain how the two cause a response
- AMPA receptors mediate the initial fast depolarisation
- NMDA receptors permeable to Ca2+
- NMDA receptors need glutamate to bind to depolarise the cell and allow ions to flow through the channel
- GLYCINE acts as a co-agonist
- Glutamate alone not enough as Mg2+ ions block the pore
- Activation of AMPA receptors causes Mg2+ to move out of the pore
How are glutamate receptors involved in learning and memory?
- Activation of NMDA receptors (and mGluRs) can up-regulate AMPA receptors
- Strong, high frequency stimulation causes long term potentiation
- Ca2+ entry through NMDA receptors important for induction of LTP
- However, too much calcium through NMDA can cause excitotoxicity
What are the 2 inhibitory amino acid neurotransmitters?
- GABA - main inhibitory in brain
- Glycine acts as inhibitor mainy in the brainstem & spinal cord
Describe the type of receptors for GABAA and Glycine
Both have integral Cl- channels
Opening the channel causes hyperpolarisation → decreased action potential firing
How do barbiturates and benzodiazepines elicit their effects at GABAA receptors?
Both bind to GABAA enhancing the response to GABA → don’t open the channel themselves but get a bigger and longer response when GABA is present
Barbiturates - anxiolytic and sedative action (rarelt used as risk of fatal overdose, dependence and tolerance)
Benzodiazepines - have sedative and anxiolytic effects, used to treat anxiety, insomnia and epilepsy
What is the role of glycinergic interneurones in the spinal cord and brainstem?
Involved in reflexes e.g. patellar jerk reflex
Every contraction needs a relaxation
