Exam 2 - glutamate and GABA

Question 1

Glutamate/aspartate

Answer 1

principle excitatory NTs

Question 2

Glutamate plays a specific functional role in

Answer 2

synaptic plasticity

Question 3

What does the NMDA receptor not do?

Answer 3

it is not blocked by NBQX

Question 4

Which drug does not enhance the effects of GABA on the GABAa receptor?

Answer 4

DBIs

Question 5

Glutamate synthesis

Answer 5

• glutamate can be derived from metabolic breakdown of glucose
• precursor glutamine that uses catalyst enzyme glutaminase

Question 6

These transporters are in charge of the release of glutamate:

Answer 6

• EAAT1-EAAT5
• EAAT1 and EAAT2 are located on astrocytes

Question 7

What proteins are in charge of the reuptake of glutamate?

Answer 7

VGLUT1, 2, and 3

Question 8

ALS results in the death of what kind of neurons?

Answer 8

glutamate

Question 9

Glutamatergic system

Answer 9

• glutamate is used by all pyramidal neurons
• innervate the striatum, thalamus, and limbic system
• important for excitatory pathways

Question 10

What is unique about the NMDA receptor?

Answer 10

• the only receptor that is both a sodium and calcium channel
• requires both glutamate and glycine or D-serine
• is an ionotropic receptor that also has secondary messenger characteristics

Question 11

Ionotropic glutatmate receptors

Answer 11

• AMPA (sodium channel), Kainate (sodium channel), and NMDA (sodium and calcium channel)
• only receptors that causes depolarization

Question 12

NBQX

Answer 12

• antagonist of AMPA and kainate receptors (glutamate receptors)
• causes sedation and reduced locomotor activity
• protects against induced seizures

Question 13

Metabotropic glutamate receptors

Answer 13

• MGluR1-mGluR8
• some inhibit CAMP, others activate phosphoinositide second messenger system

Question 14

MGluR1 receptor

Answer 14

important for locomotor activity, motor coordination, and learning

Question 15

NMDA receptors play an important role in:

Answer 15

learning and memory

Question 16

What is LTP and which receptor is important for LTP?

Answer 16

• long term potentiation
• NMDA

Question 17

Doogie mouse

Answer 17

• overexpresses the NR2B subunit of the NMDA receptor
• shows enhanced LTP and better performance on morris water maze and novel object recognition task

Question 18

Object recognition

Answer 18

subject has to remember which object is old and which is new, and will spend more time investigating the new object

Question 19

Administering glutamate into a brain structure is (glutamate excitotoxicity)?

Answer 19

toxic, high concentrations cause cell death

Question 20

Apoptosis

Answer 20

programmed cell death, cell shrivels up

Question 21

Necrosis

Answer 21

cell death, cell swells and eventually explodes

Question 22

Excitotoxicity in humans in exhibited when?

Answer 22

• ingesting domoic acid through seafood
• causes headache, dizziness, muscle weakness, mental confusion, and can result in death

Question 23

Brain ischemia

Answer 23

disruption of blood supply to the brain
- focal - blockage in one area
- global - blockage to entire brain
- most damage is due to excess glutamate release

Question 24

GABA and glycine

Answer 24

inhibitory NTs

Question 25

GABA synthesis, what is synthesis blocked by?

Answer 25

- synthesized in a single step - glutamate is the precursor, and GAD is the catalyst enzyme - allylglycine - causes seizures

Question 26

What is GABA loaded into vesicles by? What is it removed from the synaptic cleft by?

Answer 26

- VGAT - GAT-1,2, and 3

Question 27

GAT-1

Answer 27

- one of GABA's receptors - inhibitor is Tiagabine - used to treat patients with epilepsy - inhibition causes seizures

Question 28

For every one GABA that is broken down, how many are made?

Answer 28

1

Question 29

Where is GABA mainly found?

Answer 29

cerebral cortex, hippocampus, substantia nigra, and spinal cord

Question 30

GABAa receptors

Answer 30

- has binding sites for all inhibitors - ionotropic - hyperpolarizing (chloride channel)

Question 31

Muscimol

Answer 31

- GABAa agonist - found in mushrooms, and have stimulatory and hallucinogenic qualities - cause hyperthermia, altered appetite, repeated visions, similar effects to LSD

Question 32

GABAa antagonists

Answer 32

- bicuculline and picrotoxin (non-competitive) - both block the binding of GABA, causing seizures

Question 33

Anxiolytic drugs

Answer 33

- antianxiety drugs with anticonvulsant properties (benzodiazepines) - alcohol has similar properties to them

Question 34

Seizures

Answer 34

random firing of neurons in the brain, consequence of interrupted GABA activity

Question 35

Seizure disorders

Answer 35

brain disorder with an enduring predisposition to generate epileptic seizures

Question 36

What are the two main types of seizures?

Answer 36

- generalized - involves entire brain - partial - only a specific area of the brain is affected

Question 37

What are the types of partial seizures?

Answer 37

- simple: motor or sensory, pt. remains conscious - complex: impairment of consciousness, out of context behaviors (automatisms)

Question 38

What are the types of generalized seizures?

Answer 38

- also called grand mal seizures, cause a change in consciousness - tonic/clonic major convulsions, rigidity and jerks, loss of consciousness - atonic: lapse of muscle tone - myoclonic: brief jerks lasting not more than a second or two - status epilepticus: series of seizures lasting >30 minutes, several grand mal seizures in a row, can cause damage to the hippocampus

Question 39

Absence seizure

Answer 39

- petit mal seizures - person appears to be staring into space with or without jerking or twitching movements - common in children

Question 40

How are seizures diagnosed?

Answer 40

- seizure type - etiology - age of onset - EEG - seizures associated with high amplitude spikes

Question 41

Treatment of seizures

Answer 41

- anticonvulsants, which often act upon GABAa - surgery in extreme cases

Question 42

GABAb receptors

Answer 42

- inhibit CAMP formation and stimulate K+ channel opening - common agonist is baclofen, which is given to patients with muscle spasticity

Question 43

Drugs that act on the GABAa receptor can or cannot also act of the GABAb receptor?

Answer 43

cannot