Neurotransmitter System I: Glutamate

Question 1

What are the criteria for a neurotransmitter?

Answer 1

Synthesised and stored in the pre-synaptic neuron
Release by a presynaptic axon terminal upon stimulation
Produce a response in the post-synaptic cell

Question 2

What is glutamate?

Answer 2

major excitatory neurotransmitter in the CNS

Question 3

What do over half of all the brain synapses release?

Answer 3

Glutamate

Question 4

What is glutamate synthesised from, and using what enzyme?

Answer 4

Glutamine, using glutaminase

Question 5

Where is glutamate synthesised?

Answer 5

Nerve terminals

Question 6

How is glutamate transported into vesicles?

Answer 6

Counter transport with H+ ions using VGLUTs

Question 7

How is glutamate retaken up?

Answer 7

Sodium ion dependant excitatory amino acid transporters

Question 8

What enzyme degrades glutamate?

Answer 8

Glutamine synthase

Question 9

How is glutamine transported out of the glial cell and into the neurons?

Answer 9

SN1 and SAT2 transporters

Question 10

What are the ionotropic glutamate receptors?

Answer 10

AMPA, NMDA, Kainate

Question 11

What are the metabotropic glutamate receptors?

Answer 11

Group I, II and III

Question 12

What do NMDA receptors allow the entry of?

Answer 12

Both sodium and calcium ions

Question 13

What do AMPA and Kainate receptors allow the entry of?

Answer 13

Sodium

Question 14

What do AMPA, NMDA and kainate receptors allow out?

Answer 14

Potassium

Question 15

What are the four AMPA receptor subunit types?

Answer 15

GluA 1, 2, 3 and 4

Question 16

What is the most common makeup of an AMPA receptor?

Answer 16

Two GluA 2 subunits and two GluA 1, 3, or 4

Question 17

How many binding sites does the AMPA receptor have?

Answer 17

Four

Question 18

How many binding sites must be occupied for AMPA channel opening?

Answer 18

Two

Question 19

What prevents calcium ion flow in AMPA receptors?

Answer 19

GluA2 subunit

Question 20

What are the subunit types for NMDA?

Answer 20

GluN 1, 2 and 3

Question 21

What is the most common NMDA structure?

Answer 21

Two GluN1 and two GluN2

Question 22

What is special about GluN3 subunits?

Answer 22

Nonfunctional and therefore inhibitory to NMDA receptor function

Question 23

Are the NMDA receptors ligand or voltage gated?

Answer 23

Both

Question 24

What blocks the voltage gated NMDA channels at resting membrane potential?

Answer 24

Magnesium

Question 25

What are the subunit types for Kainate receptors?

Answer 25

GluK 1, 2, 3, 4 and 5

Question 26

Which kainate receptors can form homomers or heteromers?

Answer 26

GluK 1- 3

Question 27

Which Kainate receptors can only form heteromers with GluK 1-3?

Answer 27

GluK 4-5

Question 28

What is required for opening of the kainate ligand gated ion channel?

Answer 28

Glutamate binding

Question 29

What are metabotropic glutamate receptors made up of?

Answer 29

Large extracellular domain 7 TMDs Intracellular C terminal domain

Question 30

What are the subtypes of metabotropic glutamate receptors?

Answer 30

MGlu 1-8

Question 31

What metabotropic glutamate receptor subtypes are in group I?

Answer 31

MGlu 1 and 5

Question 32

What metabotropic glutamate receptor subtypes are in group II?

Answer 32

MGlu 2 and 3

Question 33

What metabotropic glutamate receptor subtypes are in group III?

Answer 33

MGlu 4, 6, 7 and 8

Question 34

What are the group I metabotropic glutamate receptors coupled to?

Answer 34

The Gq/PIP2 receptor pathway

Question 35

What does the Gq/PIP2 receptor pathway lead to?

Answer 35

Calcium release

Question 36

What are group I metabotropic glutamate receptors important in?

Answer 36

Synaptic plasticity

Question 37

Where are group I metabotropic glutamate receptors predominantly found?

Answer 37

Post synaptic

Question 38

What are the group II and III metabotropic glutamate receptors coupled to?

Answer 38

Gi/O pathway

Question 39

What does the Gi/O pathway do?

Answer 39

Decreases cAMP formation and inhibits neurotransmitter release

Question 40

Where are group II and III metabotropic glutamate receptors predominantly found?

Answer 40

Pre-synaptic

Question 41

What do excitatory neurotransmitters lead to?

Answer 41

Neuronal membrane depolarisation

Question 42

What do excitatory post synaptic currents represent?

Answer 42

The flow of ions and change in current across a post-synaptic membrane

Question 43

What does a change in current across a post-synaptic membrane lead to?

Answer 43

The generation of excitatory postsynaptic potentials

Question 44

What does the generation of excitatory postsynaptic potentials increase?

Answer 44

The likelihood of firing an action potential

Question 45

What is the difference between excitatory post synaptic currents in NMDA, AMPA and kainate?

Answer 45

NMDA and kainate are slower and last longer than those produced by AMPA receptors

Question 46

What is excitotoxicity?

Answer 46

Pathological process by which excessive excitatory stimulation can lead to neuronal damage and death

Question 47

What happens if VGLUTs aren't working properly?

Answer 47

Glutamate accumulates in the presynaptic neurone

Question 48

What normally stops glutamate accumulating in the synaptic cleft?

Answer 48

EAATs transport glutamate out of the synaptic cleft into the presynaptic neuron down the concentration gradient

Question 49

What happens to EAAT function if there's a high glutamate concentration in the presynaptic neuron?

Answer 49

Starts pumping glutamate into the synaptic cleft

Question 50

What happens if glutamate is pumped into the synaptic cleft?

Answer 50

Uncontrolled influx of calcium into the post-synaptic neuron

Question 51

What can uncontrolled influx of calcium into the post-synaptic neuron cause?

Answer 51

Mitochondrial damage, oxidative stress and apoptosis

Question 52

What diseases are linked to excitotoxicity?

Answer 52

Stroke and Alzheimer's

Question 53

What is Alzheimer's?

Answer 53

Neurodegenerative disorder

Question 54

What is Alzheimer's characterised by?

Answer 54

Neuronal cell death in the hippocampus and cerebral cortex

Question 55

What is the drug used to treat moderate-severe Alzheimer's called?

Answer 55

Memontine

Question 56

How does memontine work?

Answer 56

Low affinity NMDA receptor antagonist that blocks the NMDA receptor ion channel to reduce glutamate excitotoxicity

Question 57

What is long term potentiation?

Answer 57

Persistent strengthening of a synapse based upon repeated patterns of activity

Question 58

What does long term potentiation underlie?

Answer 58

Learning and memory