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PSYCH 478 > Glutamate > Flashcards

Glutamate Flashcards

1
Q

TRUE or FALSE: non-essential amino acids are not required in diet

A

TRUE

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2
Q

Where are non-essential amino acids synthesized?

A

most cells of the body

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3
Q

What are the 2 functional groups of the amino acid NTs?

A
  • excitatory AA NT: glutamate, aspartate
  • inhibitory AA NT: GABA, glycine
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4
Q

TRUE or FALSE: aspartate is released in a Na+ dependent manner

A

FALSE: Ca2+ dependent manner

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5
Q

TRUE or FALSE: Aspartate is stored in vesicles

A

False: just in the cytoplasm, not in vesicles

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6
Q

Which receptors does aspartate act on?

A

glutamate receptors

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7
Q

What is the most widely used excitatory NT?

A

glutamate

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8
Q

What percentage of neruons and synapses are glutamatergic?

A
  • 90% of neurons
  • 80-90% of synapses
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9
Q

What does glutatmate mediate?

A

fast excitatory neurotransmission (sensory, motor, emotion, cognition, memory)

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10
Q

Where is glutatmate most concentrated in the neuron?

A

presynaptic compartments

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11
Q

Describe the synthesis of glutamate (i.e. what enzyme)

A

glutamine converted to glutamate by glutaminase

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12
Q

How many families are there of VGLUT?

A

3

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13
Q

Glutamate is packaged into ______ to maintain a separate pool of NT.

A

vesicles

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14
Q

What can be used to identigy glutamatergic neurons?

A

vesicular glutamate transporter (VGLUT)

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15
Q

TRUE or FALSE: VGLUT is structurally and functionally similar to VMAT

A

TRUE

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16
Q

What is glutamate metabolized by? What is the end product?

A

glutamate converted to glutamine by glutamine synthetase

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17
Q

What are responsible for reuptake of glutamate?

A

excitatory AA transporters (EAATs)

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18
Q

TRUE or FALSE: EAATs are specific for glutamate

A

FALSE: non-specific fro glutamate and aspartate

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19
Q

How many families of EAATs are there?

A

5

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20
Q

Neurons comprise only _____% of the cells in the CNS. The reminains cells are termed ________.

A

50; glia

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21
Q

What are astrocytes?

A

define the brain side of the BBB

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22
Q

What are oligodendrocytes?

A

myelinate axons in white matterW

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23
Q

What are ependymal cells?

A

generate and regulate CSF

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24
Q

What are microglia?

A

immune surveillance and development

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25
What do astrocytes regulate?
- intake of nutrients and O2 and blood flow in the brain - synaptic functions and plasticity
26
What kind of synapses are astrocytes coupled by?
electrical synapses - gap junctions
27
TRUE or FALSE: human astrocytes are very dfiferent from rodents
TRUE
28
Grafting human astrocytes into mouse cortex ________ cognitive measures.
increases
29
Where are VGLUT1 and 2 expressed?
distinct glutamatergic populations in the CNS
30
Where is VGLUT3 expressed?
GABAergic, cholinergic, and monoaminergic neurons (modulatory function)
31
TRUE or FALSE: high levels of extracellular glutamate are toxic to neurons
TRUE
32
What does genetic KO of EAAT 1 and 2 result in?
increases in glutamate, esp in the striatum
33
What does KO of EAAT3 result in?
more limited effects in comparison to EAAT1 and 2
34
Which EAAT(s) is/are associated with astrocytes vs neurons?
- EAAT1 and 2 = astrocytic - EAAT 3 = neuronal
35
Which pathway of glutamate recycling is the dominant pathway? (neuron or astrocyte?)
astrocyte
36
Abnormality of which EAAT is observed in ALS?
EAAT2
37
glutamatergic synapses are wrapped by __________ ___________ expressing ______________ and ___________.
astrocyte processes; EAAT1, EAAT2
38
TRUE or FALSE: glutamate uptake into astrocytes is slow and inefficient.
FALSE: rapid and high efficiency
39
What is the principal site of glutamate breakdown?
astrocyte
40
Describe the recycling of glutamate in the synapse?
glutamine is exported from astrocytes and taken up into neurons to be converted back to glutamate
41
What kind of synapse is there for glutamate?
tripartite synapse
42
What substance can be used experimentally to induce glutamatergic lesions?
MSG
43
TRUE or FALSE: MSG is proposed as one of the 5 basic tastes (salty)
FALSE: umami
44
MSG acts on glutamate receptors on the _______.
tongue
45
Is MSG syndrome real?
no
46
Where are EAAT1 and 2 expressed?
astrocytes
47
Where are EAAT3 and 4 expressed?
neurons
48
Where are EAAT5 expressed?
retina
49
What kind of neurons of the cerebral cortex are involved in glutatmatergic signaling?
pyramidal neurons
50
Which tracts are glutamatergic?
corticospinal tract (voluntary motor control)
51
Which fibers of the cerebellum are glutamatergic?
parallel fibers (excitatoary inputs to Purkinje cells)
52
Which brain structure inovlved in memory is highly associated with glutamatergic signalling?
hippocampus
53
What are the glutamatergic ionotropic receptors?
AMPA, kainate, NMDA
54
TRUE or FALSE: glutamate is repsonsible for FAST excitiatory synaptic transmission
TRUE
55
TRUE or FALSE: AMPA receptors are selective for Na+
FALSE: non-selective cation channel (Na+ and K+)
56
How many subunits of AMPA receptors are there? What do they form?
- 4 types (GluR1-4) - heterotetramers (dimers of dimers)
57
TRUE or FALSE: AMPA receptors have slow kinetics
FALSE: rapid
58
What results from a mutation in AMPAR GRIN2A gene?
58% decrease in Parkinson's risk, if also a heavy coffee drinker
59
Which receptor are kainate receptors functionally similar to?
AMPA receptors
60
How many subunits of kainate receptors are there?
5 subunits
61
What is the selective agonist of kainate receptors? Where is it isolated from?
kainate, isolated from red seaweek
62
TRUE or FLASE: kainate receptors are faster than AMPAR
FALSE: slower than AMPAR
63
Where can kainate receptors be expressed presynaptically?
GABAergic synapses
64
TRUE or FALSE: kainate receptors hav e a limited role in fast, excitatory transmission
TRUE
65
Which two excitatory receptors are difficult to distinguish experimentally?
kainate and AMPA receptors
66
What do agonists at kainate and AMPA receptors cause?
seizures
67
What is used as a model of epilepsy?
kainic acid
68
How can you experiemtnally induce spontaneous seizures?
repeated administration of kainic acid
69
What are the agonists of AMPA and Kainate? Describe the selectivity.
- kainate/kainic acid - kainate receptor - AMPA - AMPAR - domoic acid - kainate receptor
70
What does domoic acid cause in humans?
amnesiac shellfish poisoning
71
What are the antagonists of kainate and AMPA receptors? What is the selectivity?
- NBQX - AMPAR - NS102 - kainate receptor
72
TRUE or FALSE: glutamatergic synaptic transmission eleicits excitatory postysnaptic potentials (EPSP)
TRUE
73
What ions are NMDA receptors permeable to?
Na+, K+, Ca2+
74
What ions are AMPARs permeable to?
Na+ and K+
75
Where are NMDA receptors found?
widely distributed: cortex, huppocampus, basal ganglia, septum, cerebellum
76
What are NMDARs always co-expressed with?
either AMPA or kainate receptors
77
How many binding sites are there for NMDARs
6 - highly regulated
78
NMDARs are important in ________ and ________ processes by modulating ______ ______.
learning and memory; synaptic strength
79
What are the obligatory agonist binding sites of NMDAR?
glutamate and glycine/D-serine sites
80
Describe NMDAR gating
- Mg2+ occupies NMDAR channel pore - agonist binding alone cannot open the channel - previously present depolarization displaces Mg2+ (voltage-dependent) - NMDAR only active after initial depolarization (through AMPAR)
81
What are the endogenous agonists of NMDAR?
- glutamate and glycine/D-serine (obligatory) - polyamines - allosteric modulators
82
What are the exogenous agonists of NMDAR?
NMDA - synthetic AA
83
What are the endogenous antagonists of NMDAR?
Zn2+ (allosteric), Mg2+
84
What are the exogenous antagonists of NMDAR?
MK801, PCP, ketamine
85
What is MK801 used for? Is it competitive or non-competitive?
- widely used experimental antagonist of NMDAR - non-competitive
86
What is the function of PCP and ketamine? Are they competitive or non-competitive?
- dissociative anesthetics/recreational - non-competitive
87
What is the significance of the polyamine binding site of NMDAR?
site of endogenous allosteric modulation (positive)
88
What is the significance of the Mg2+, Zn2+, and H+ binding sites?
- Mg2+ - voltage-dependent bloc of channel opening - Zn2+ - negative allosteric modulation site - H+ - pH sensitive egative modulation
89
Why is NMDA described as a coincidence detector?
opens only under conditions of strong or repeated stimulation

PSYCH 478 (28 decks)

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