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PSYCH 478 > Glutamate > Flashcards

Glutamate Flashcards

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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
Q

What do astrocytes regulate?

A
  • intake of nutrients and O2 and blood flow in the brain
  • synaptic functions and plasticity
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26
Q

What kind of synapses are astrocytes coupled by?

A

electrical synapses - gap junctions

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27
Q

TRUE or FALSE: human astrocytes are very dfiferent from rodents

A

TRUE

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28
Q

Grafting human astrocytes into mouse cortex ________ cognitive measures.

A

increases

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29
Q

Where are VGLUT1 and 2 expressed?

A

distinct glutamatergic populations in the CNS

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30
Q

Where is VGLUT3 expressed?

A

GABAergic, cholinergic, and monoaminergic neurons (modulatory function)

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31
Q

TRUE or FALSE: high levels of extracellular glutamate are toxic to neurons

A

TRUE

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32
Q

What does genetic KO of EAAT 1 and 2 result in?

A

increases in glutamate, esp in the striatum

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33
Q

What does KO of EAAT3 result in?

A

more limited effects in comparison to EAAT1 and 2

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34
Q

Which EAAT(s) is/are associated with astrocytes vs neurons?

A
  • EAAT1 and 2 = astrocytic
  • EAAT 3 = neuronal
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35
Q

Which pathway of glutamate recycling is the dominant pathway? (neuron or astrocyte?)

A

astrocyte

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36
Q

Abnormality of which EAAT is observed in ALS?

A

EAAT2

37
Q

glutamatergic synapses are wrapped by __________ ___________ expressing ______________ and ___________.

A

astrocyte processes; EAAT1, EAAT2

38
Q

TRUE or FALSE: glutamate uptake into astrocytes is slow and inefficient.

A

FALSE: rapid and high efficiency

39
Q

What is the principal site of glutamate breakdown?

A

astrocyte

40
Q

Describe the recycling of glutamate in the synapse?

A

glutamine is exported from astrocytes and taken up into neurons to be converted back to glutamate

41
Q

What kind of synapse is there for glutamate?

A

tripartite synapse

42
Q

What substance can be used experimentally to induce glutamatergic lesions?

A

MSG

43
Q

TRUE or FALSE: MSG is proposed as one of the 5 basic tastes (salty)

A

FALSE: umami

44
Q

MSG acts on glutamate receptors on the _______.

A

tongue

45
Q

Is MSG syndrome real?

A

no

46
Q

Where are EAAT1 and 2 expressed?

A

astrocytes

47
Q

Where are EAAT3 and 4 expressed?

A

neurons

48
Q

Where are EAAT5 expressed?

A

retina

49
Q

What kind of neurons of the cerebral cortex are involved in glutatmatergic signaling?

A

pyramidal neurons

50
Q

Which tracts are glutamatergic?

A

corticospinal tract (voluntary motor control)

51
Q

Which fibers of the cerebellum are glutamatergic?

A

parallel fibers (excitatoary inputs to Purkinje cells)

52
Q

Which brain structure inovlved in memory is highly associated with glutamatergic signalling?

A

hippocampus

53
Q

What are the glutamatergic ionotropic receptors?

A

AMPA, kainate, NMDA

54
Q

TRUE or FALSE: glutamate is repsonsible for FAST excitiatory synaptic transmission

A

TRUE

55
Q

TRUE or FALSE: AMPA receptors are selective for Na+

A

FALSE: non-selective cation channel (Na+ and K+)

56
Q

How many subunits of AMPA receptors are there? What do they form?

A
  • 4 types (GluR1-4)
  • heterotetramers (dimers of dimers)
57
Q

TRUE or FALSE: AMPA receptors have slow kinetics

A

FALSE: rapid

58
Q

What results from a mutation in AMPAR GRIN2A gene?

A

58% decrease in Parkinson’s risk, if also a heavy coffee drinker

59
Q

Which receptor are kainate receptors functionally similar to?

A

AMPA receptors

60
Q

How many subunits of kainate receptors are there?

A

5 subunits

61
Q

What is the selective agonist of kainate receptors? Where is it isolated from?

A

kainate, isolated from red seaweek

62
Q

TRUE or FLASE: kainate receptors are faster than AMPAR

A

FALSE: slower than AMPAR

63
Q

Where can kainate receptors be expressed presynaptically?

A

GABAergic synapses

64
Q

TRUE or FALSE: kainate receptors hav e a limited role in fast, excitatory transmission

A

TRUE

65
Q

Which two excitatory receptors are difficult to distinguish experimentally?

A

kainate and AMPA receptors

66
Q

What do agonists at kainate and AMPA receptors cause?

A

seizures

67
Q

What is used as a model of epilepsy?

A

kainic acid

68
Q

How can you experiemtnally induce spontaneous seizures?

A

repeated administration of kainic acid

69
Q

What are the agonists of AMPA and Kainate? Describe the selectivity.

A
  • kainate/kainic acid - kainate receptor
  • AMPA - AMPAR
  • domoic acid - kainate receptor
70
Q

What does domoic acid cause in humans?

A

amnesiac shellfish poisoning

71
Q

What are the antagonists of kainate and AMPA receptors? What is the selectivity?

A
  • NBQX - AMPAR
  • NS102 - kainate receptor
72
Q

TRUE or FALSE: glutamatergic synaptic transmission eleicits excitatory postysnaptic potentials (EPSP)

A

TRUE

73
Q

What ions are NMDA receptors permeable to?

A

Na+, K+, Ca2+

74
Q

What ions are AMPARs permeable to?

A

Na+ and K+

75
Q

Where are NMDA receptors found?

A

widely distributed: cortex, huppocampus, basal ganglia, septum, cerebellum

76
Q

What are NMDARs always co-expressed with?

A

either AMPA or kainate receptors

77
Q

How many binding sites are there for NMDARs

A

6 - highly regulated

78
Q

NMDARs are important in ________ and ________ processes by modulating ______ ______.

A

learning and memory; synaptic strength

79
Q

What are the obligatory agonist binding sites of NMDAR?

A

glutamate and glycine/D-serine sites

80
Q

Describe NMDAR gating

A
  • 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
Q

What are the endogenous agonists of NMDAR?

A
  • glutamate and glycine/D-serine (obligatory)
  • polyamines - allosteric modulators
82
Q

What are the exogenous agonists of NMDAR?

A

NMDA - synthetic AA

83
Q

What are the endogenous antagonists of NMDAR?

A

Zn2+ (allosteric), Mg2+

84
Q

What are the exogenous antagonists of NMDAR?

A

MK801, PCP, ketamine

85
Q

What is MK801 used for? Is it competitive or non-competitive?

A
  • widely used experimental antagonist of NMDAR
  • non-competitive
86
Q

What is the function of PCP and ketamine? Are they competitive or non-competitive?

A
  • dissociative anesthetics/recreational
  • non-competitive
87
Q

What is the significance of the polyamine binding site of NMDAR?

A

site of endogenous allosteric modulation (positive)

88
Q

What is the significance of the Mg2+, Zn2+, and H+ binding sites?

A
  • Mg2+ - voltage-dependent bloc of channel opening
  • Zn2+ - negative allosteric modulation site
  • H+ - pH sensitive egative modulation
89
Q

Why is NMDA described as a coincidence detector?

A

opens only under conditions of strong or repeated stimulation

PSYCH 478 (28 decks)

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