The Role of Neurones and Glia

Question 1

Name the glial cells located within the CNS

Answer 1

• Astrocytes
• Oligodendrocytes
• Microglia

Question 2

State the actions of astrocytes

Answer 2

• Structural support
• Help to provide nutrition for neurones
• Remove neurotransmitters
• Maintain ionic environment (K+ buffering)
• Help to form blood brain barrier

Question 3

Explain how and why astrocytes provide nutrition for neurones

Answer 3

• Neurones have high energy demands
  
  • Glucose is transported through GLUT3 into the neurons from the blood
  • Neurones do not store or produce glycogen
• Astrocytes produce lactate which can be transferred to neurones
  
  • Supplements their supply of glucose if glucose transport not enough
  • Glucose lactate shuttle moves lactate into the neuron to produce energy
  • However lactate is only a limited store - only 10-15 min supply of glucose

Question 4

Outline how astrocytes remove neurotransmitters

Answer 4

• Control concentration of neurotransmitters
  
  • Astrocytes have transporters for transmitters which re-uptake them
• Glutamate needs to be controlled to stop postsynaptic response, stop spread to other areas and to reduce concentration as glutamate is toxic
• Glutamate is re-uptaken by astrocytes and converted to glutamine, which is then transported back into vesicles for synaptic transmission

Question 5

Outline how and why astrocytes maintain ionic environment of CNS

Answer 5

• High levels of neuronal activity could lead to arise in [K+] in brain ECF
  
  • When many action potentials fire, Na enters neurons and K exits through Na/K ATPase
  • Leads to a rise in [K+] in the brain ECF, which can cause further neurones to depolarise or inappropriate action potential firing leading to epilepsy
• Astrocyte take up K+ to prevent this
  
  • Low concentration of K inside astrocyte, so K enters through K channels and transporters

Question 6

State the action of oligodendrocytes

Answer 6

• Responsible for myelinating axons in CNS

- Myelin sheath targeted by antibodies in multiple sclerosis

Question 7

State the action of microglia

Answer 7

• Immunocompetent cells which recognize foreign material and become activated
• When activated, it changes shape and processes to becomes phagocytic
  - Also act as antigen presenting cells to T-cells

Question 8

Outline the purpose of the blood brain barrier

Answer 8

• Maintains the correct environment for neurones
• Limits diffusion of substances from the blood to the brain extracellular fluid
• K entering due to high plasma concentration can affect depolarisation of neurones
• Amino acids entering after a meal can act as neurotransmitter

Question 9

Describe the structure of the blood brain barrier

Answer 9

• Brain capillaries have tight junctions between endothelial cells
• Basement membrane surrounds brain capillary
• End feet of astrocyte processes surround capillaries, which promote tight junctions to form

Question 10

State how substances are transported across the blood brain barrier

Answer 10

• Substances such as glucose, amino acids and ions are transported across the blood brain barrier
• Glucose transported through GLUT1
• Water, CO2 and oxygen can freely move between the blood brain barrier

Question 11

Describe what immune privilege is

Answer 11

• Normal inflammatory response not ideal within the CNS as skull is rigid and will not tolerate volume expansion
• Microglia act as antigen presenting cells
• T-cells can enter the CNS
  - However CNS inhibits the initiation of the pro-inflammatory T-cell response

Question 12

Describe how signals are transmitted through a synapse

Answer 12

• Depolarisation in the presynaptic terminal opens voltage gated Ca2+ channels, allowing Ca2+ ions to enter the terminal
• Allows vesicles containing neurotransmitter to fuse with the presynaptic terminal membrane and release transmitter
• Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane

Question 13

State the main excitatory and inhibitory amino acid neurotransmitters

Answer 13

• Excitatory - glutamate

- Inhibitory - GABA, glycine

Question 14

Describe the types of glutamate receptors

Answer 14

• Glutamate receptors can be ionotropic (ligand gated ion channel) or metabotropic (G-protein)
• Ionotropic receptors include AMPA receptors NMDA receptors
  
  • AMPA receptors are permeable to Na and K
  • NMDA receptors permeable to Na, K and Ca
• Metabotropic receptors linked to either changes in IP3 and Ca mobilisation or inhibition of adenylyl cyclase and decreased cAMP levels

Question 15

Explain excitatory postsynaptic potential (EPSP)

Answer 15

• Fast excitatory neurotransmitters cause depolarisation of the postsynaptic cell by acting on ligand-gated ion channels
• Excitatory postsynaptic potential (EPSP) - depolarisation causes more action potentials

Question 16

Describe the receptors acting at glutamatergic synapses

Answer 16

• Glutamatergic synapses have both AMPA and NMDA receptors
• AMPA receptors mediate the initial fast depolarisation
• NMDA receptors are permeable to Ca2+ and normally blocked by Mg2+
• NMDA receptors need glutamate to bind and the cell to be depolarised to allow ion flow through the channel
  
  • Pushes Mg2+ away from receptor to allow ion flow through channel
    
    • Glycine acts as a co-agonist

Question 17

Describe the role of glutamate receptors in inducing long term potentiation

Answer 17

• Glutamate receptors have an important role in learning and memory
• Activation of NMDA receptors can up-regulate AMPA receptors
• Strong, high frequency stimulation causes long term potentiation (LTP)
• Ca2+ entry through NMDA receptors important for induction of LTP

Question 18

State the consequence of too much Ca2+ entry through NMDA receptors

Answer 18

• Too much Ca2+ entry through NMDA receptors causes excitotoxicity - toxic environment due to excessive action potential firing
  
  • Eg. Damaged area of brain (stroke) releases K, which diffuses and depolarises to surrounding area
• Causes many action potentials to form and release glutamate, which kills neurones around infarct area
• Glutamate is very toxic and needs to be removed by glial cells

Question 19

Explain inhibitory postsynaptic potential (IPSP)

Answer 19

• GABAa and glycine receptors have integral Cl channels

- Opening the Cl channel causes hyperpolarisation - inhibitory post-synaptic potential (IPSP)

Question 20

Describe drugs which target GABA receptors

Answer 20

• Barbiturates and benzodiazepines bind to GABAA receptors and enhance response to GABA
• Barbiturates - anxiolytic and sedative actions
  
  • Sometimes used as anti-epileptic drugs
• Benzodiazepines - anxiolytic and sedative effects
  - Used to treat anxiety, insomnia, epilepsy

Question 21

Describe the different locations of GABA and glycine uses

Answer 21

• GABA main inhibitory transmitter in the brain

- Glycine acts mainly in the brainstem and spinal cord

Question 22

Describe the action of glycine in the patellar tendon reflex

Answer 22

• When patellar tendon hit, it is detected by muscle spindles in quadriceps muscle
• Sends afferent signals to the CNS, where glutamate sends EPSP through the motor neuron to nACh receptors in the leg causing contraction of quadriceps
• Afferent signals also synapse with interneurons in CNS and releases glycine, which sends IPSP along motor neurons to reciprocal muscle in the leg causing relaxation of hamstring

Question 23

State the main biogenic amine neurotransmitters

Answer 23

• Includes acetylcholine, dopamine, noradrenaline, serotonin (5-HT)
• Mostly act as neuromodulators and confined to specific pathways

Question 24

Outline L-DOPA and how Parkinson’s disease can be treated with it

Answer 24

• L-DOPA (levodopa) is a precursor to dopamine which can be transporter through the blood brain barrier
  
  • Activated by AADC to become dopamine
• Can be treated with levodopa (L-DOPA) and carbidopa
  
  • Carbidopa given to inhibit AADC - prevents breakdown of L-DOPA in the peripheral system
  • Carbidopa cannot cross the blood brain barrier - does not prevent dopamine activation in the brain