Deck 8: Glutamate and Gaba

Question 1

Which statement about astrocytes is false?

A) They contain glutamine synthetase.
B) They remove glutamate from the extracellular fluid.
C) They prevent excessive neuronal excitation and degeneration.
D) They use the transporter EAAT3.

Answer 1

D

Question 2

VGLUT proteins

A) are found in all cells containing glutamate.
B) take up glutamate from the synaptic cleft.
C) are identical to the plasma membrane transporters.
D) come in three different forms that show little overlap in location.

Answer 2

D

Question 3

The findings from VGLUT knockout mice suggest that

A) VGLUT2-expressing neurons are critical for survival.
B) VGLUT2-expressing neurons have no impact on offspring survival.
C) VGLUT1 and VGLUT2 KO are always found in the same neurons.
D) VGLUT5 is important in the development of the auditory system.

Answer 3

A

Question 4

The presence of vesicular glutamate transporters and vesicular monoamine transporters in the same neurons suggests that

A) cells that contain a lot of glutamate must store it in multiple types of vesicles.
B) glutamate can be co-released as a neurotransmitter along with dopamine or serotonin.
C) vesicular transporters are not selective.
D) gene expression has malfunctioned in these neurons.

Question 5

_______ are responsible for removal of glutamate molecules from the extracellular fluid.

A) Excitatory amino acid transporters (EAATs)
B) Vesicular transporters (VGLUTs)
C) Vesicular inhibitory amino acid transporters (VIAATs)
D) Vesicular monoamine transporters (VMATs)

Question 6

Which statement about knockout mice lacking EAAT2 is false?

A) They have a shortened life span.
B) They develop spontaneous epileptic seizures.
C) They are more susceptible to experimentally-induced brain injury than wild-type mice.
D) They exhibit normal weight gain throughout development.

Question 7

Which primary neuronal glutamate transporter has a postsynaptic instead of a presynaptic localization?

A) EAAT1
B) EAAT2
C) EAAT3
D) EAAT5

Question 8

Glutamate differs from other neurotransmitters such as acetylcholine (ACh), dopamine (DA), and serotonin (5HT) in that

A) only specialized neurons in the brain synthesize and release it.
B) it is the only neurotransmitter that causes EPSPs.
C) it plays a role in protein synthesis and cell metabolism.
D) it can only be synthesized by a single chemical reaction.

Question 9

The AMPA receptor

A) handles most fast excitatory responses to glutamate.
B) is metabotropic.
C) opens calcium channels when activated.
D) is stimulated by the drug NBQX.

Question 10

The NMDA receptor

A) selectively opens channels for sodium, but not calcium.
B) is blocked by the antagonist NBQX.
C) has only a single binding site.
D) is responsive to both glutamate and glycine.

Question 11

Which of the following is considered to be a glutamate co-agonist at the NMDA receptor site?

A) Ketamine
B) d-Serine
C) Magnesium
D) Aspartate

Question 12

The NMDA receptor channel can be blocked by all of the following except

A) Ca²⁺ ions.
B) PCP.
C) MK-801.
D) ketamine.

Question 13

Which event does not have to occur for NMDA receptor channel opening?

A) An excitatory amino acid like glutamate must bind to the receptor.
B) The PCP block must be removed.
C) A co-agonist must bind at the glycine site.
D) The membrane must be depolarized by some other receptor.

Question 14

Drugs that work on the metabotropic glutamate receptor are of interest and under development for treating all of the following except

A) depression.
B) anxiety disorders.
C) balance and vestibular problems.
D) disorders with cognitive deficits.

Question 15

The _______ theory holds that the loss of FMRP causes exaggerated group I mGluR-related functions, including dendritic spine abnormalities and elevated long-term depression which result in the symptoms of FXS.

A) ionotropic glutamate receptor
B) metabotropic glutamate receptor
C) fragile X receptor
D) mGluR5

Question 16

Which statement correctly summarizes the translational studies using mGluR5 agonists to treat Fragile X syndrome?

A) Although mGluR5 agonists did not show promise in treating FXS in animal models, they did have efficacy in clinical trials.
B) Although mGluR5 agonists showed promise in treating FXS in animal models, they did not have efficacy in clinical trials.
C) Although the early mGlurR5 agonists did not improve FXS symptoms, a later drug, basimglurant, did.
D) mGluR5 agonists have been proven to reduce symptoms both in animal models and in people with FXS.

Question 17

A metabotropic glutamate receptor is located postsynaptically and mediates excitatory responses by stimulating the phosphoinositide second-messenger system. This receptor belongs in _______ and is either _______.

A) group I; mGluR1 or mGluR5
B) group 2; mGluR2 or mGluR3
C) group 3; mGluR4 or mGluR6
D) group 3; mGluR7 or mGluR8

Question 18

In long-term potentiation,

A) researchers apply a tetanic stimulus to the postsynaptic cell.
B) changes that involve NMDA receptors occur in the induction phase.
C) the expression phase involves kainate receptors.
D) calcium inhibits the expression of additional AMPA receptors.

Question 19

LTP is most often studied in a slice preparation from which area of the brain?

A) Cerebral cortex
B) Cerebellum
C) Thalamus
D) Hippocampus

Question 20

In the expression phase of E-LTP,

A) tetanic stimulation occurs.
B) brain-derived neurotrophic factor (BDNF) is released.
C) there is an influx of Ca²⁺ ions through the NMDA receptor.
D) AMPA receptors are removed from the membrane.

Question 21

Which process does not occur in LTP?

A) The AMPA-receptor mediated EPSP is facilitated.
B) Calcium influx activates protein kinases.
C) AMPA receptors increase in number and sensitivity.
D) NMDA receptors are highly activated during the expression phase.

Question 22

In E-LTP, what happens to silent dendritic spine synapses when functional synapses are subjected to LTP?

A) LTP leads to AMPA receptor removal from the membrane and receptor degradation.
B) There is an influx of Ca²⁺ ions into the NMDA receptor which activates AMPA receptors thereby making the silent synapses functional.
C) AMPA receptors in the silent synapses move into spine membrane thereby making the synapses functional.
D) Functional synapses suppress the transport of AMDA into silent synapses during LTP.

Question 23

The excitotoxicity hypothesis states that

A) repeated stimulation of neurons is the basis for learning and memory.
B) tetanic stimulation of the presynaptic neuron can produce LTP in the recipient cell.
C) overexposure to excitatory amino acids is cause by prolonged depolarization of receptive neurons and cell death.
D) glutamate and aspartate play a critical role in the action of drugs like PCP.

Question 24

Cell death that occurs shortly after exposure to high concentrations of glutamate and other excitatory amino acids involves

A) lysing and bursting of the cell.
B) the breakup of DNA.
C) shrinkage of the cell.
D) phagocytosis.

Question 25

Although some people experience unpleasant effects after eating the flavor enhancer monosodium glutamate (MSG) and it shows adverse effects in high doses in mice, it is generally considered safe to consume, because it

A) never reaches the brain because it breaks down in blood circulation.
B) is taken up rapidly by the vesicular transporters.
C) only affects individuals with a rare allergy.
D) does not cross the blood-brain barrier.

Question 26

Apoptosis

A) begins with swelling of the cell.
B) is a form of programmed cell death.
C) involves lysing of the cell and disintegration into the extracellular space.
D) typically indicates that a disease process has occurred.

Question 27

Glutamate plays a specific functional role in

A) synaptic plasticity.
B) anxiety reduction.
C) seizure suppression.
D) the effects of benzodiazepines.

Question 28

It is difficult to assign specific functional roles to glutamate relative to other neurotransmitters because

A) it is found throughout the brain.
B) it has very limited activity except in particular neural pathways.
C) its inhibitory action on the cortex makes it difficult to interpret.
D) it is not found in cortical neurons.

Question 29

The correct order of events in the synthesis of GABA is

A) Glutamic acid decarboxylase (GAD) $\rightarrow$ glutamate $\rightarrow$ GABA
B) Glutamate $\rightarrow$ glutamic acid decarboxylase (GAD) $\rightarrow$ GABA
C) GABA aminotransferase (GABA-T) $\rightarrow$ glutamate $\rightarrow$ GABA
D) Glutamate $\rightarrow$ GABA aminotransferase (GABA-T) $\rightarrow$ GABA

Question 30

GABA metabolism

A) takes place almost entirely in neurons.
B) is undertaken by the enzyme GABA decarboxylase.
C) is blocked by the drug GABA-T.
D) can be inhibited by the epilepsy medication vigabatrin.

Question 31

Drugs that block GAT-1, such as Gabitril (tiagabine) are useful for treating

A) memory disorders.
B) ALS.
C) seizure disorders.
D) anxiety.

Question 32

After neuronal release, what happens to GABA in the extracellular space?

A) It is removed by astrocytes.
B) It is transported by VGLUT1, VGLUT2, and VGLUT3.
C) It is removed by the transporters GAT-1, GAT-2, and GAT-3.
D) It is removed by the excitatory amino acid transporters (EAATs).

Question 33

In neurotransmitter co-release in the _______, postsynaptic cells may receive both excitatory and inhibitory inputs from the same nerve terminals thereby allowing for a _______ postsynaptic response than could be achieved using a single neurotransmitter.

A) raphe nuclei; stronger
B) lateral habenula; more fine-tuned
C) globus pallidus; more predictable
D) nucleus accumbens; more rapid

Question 34

GABA is co-expressed and co-released with the classical neurotransmitter(s)

A) glycine, acetylcholine, dopamine, and glutamate.
B) glutamate and aspartate.
C) norepinephrine and epinephrine.
D) serotonin.

Question 35

It has been suggested that abnormal firing of striatal GABAergic neurons may play a role in

A) Alzheimer's disease.
B) amyotrophic lateral sclerosis.
C) Parkinson's disease.
D) Down syndrome.

Question 36

In a patient with spinocerebellar ataxis, which is characterized by poor fine motor control and coordination, which GABA pathway is affected?

A) Purkinje cells projecting to deep cerebellar nuclei and the brainstem
B) Neural pathway from the entopeduncular nucleus to the lateral habenula
C) GABAgeric neurons projecting to the globus pallidus
D) GABAgeric neurons projecting to the sustantia nigra

Question 37

The GABA_A receptor

A) forms channels that permit chloride to move from the inside to the outside of the cell membrane.
B) is composed of four subunits labeled α, β, γ, and δ.
C) is a metabotropic receptor that inhibits cyclic AMP formation.
D) is stimulated by the intoxicating drug muscimol.

Question 38

A drug that is used to induce seizures in laboratory animals is

A) muscimol.
B) muscarine.
C) diazepam.
D) picrotoxin.

Question 39

The classic GABA_A agonist _______ comes from a fungus, and the noncompetitive GABA_A antagonist _______ comes from a plant.

A) muscimol; picrotoxin
B) muscimol; pentylenetetrazol
C) baclofen; picrotoxin
D) bicuculline; baclofen

Question 40

Which drug(s) do(es) not enhance the effects of GABA on the GABA_A receptor?

A) Ethanol
B) Baclofen
C) Benzodiazepines
D) Neurosteroids

Question 41

The α4 and α6 subunits make the GABA_A receptor insensitive to

A) barbiturates.
B) neurosteroids.
C) picrotoxin.
D) benzodiazepines.

Question 42

Benzodiazepine inverse agonist drugs would be

A) anticonvulsant.
B) anxiogenic.
C) sedating.
D) hypnotic.

Question 43

Which characteristic do neurosteroids and benzodiazepines not share?

A) They enhance GABA_A receptor function.
B) They have sedative-hypnotic effects.
C) They bind to the BDZ site on the GABA_A receptor.
D) They act as local signaling molecules.

Question 44

Anesthetics strongly enhance _______ receptor activity through an allosteric modulation of channel opening.

A) GABA_A
B) glycine
C) AMPA
D) 5-HT₃

Question 45

Which of the following is thought to be responsible for the anticonvulsant action of neurosteriods in type II (hormone withdrawal) catamenial epilepsy?

A) Upregulation of benzodiazepine receptors
B) Downregulation of benzodiazepine receptors
C) Upregulation of δ subunit-containing extrasynaptic GABA_A receptors
D) Downregulation of A5 subunit-containing extrasynaptic GABA_A receptors

Question 46

Application of GABA to brain tissue samples from people with epilepsy results in _______ instead of _______ postsynaptic responses.

A) inhibitory; excitatory
B) excitatory; inhibitory
C) delayed; immediate
D) immediate; delayed

Question 47

GABA_B receptors

A) cause potassium channel opening when stimulated.
B) are ionotropic.
C) are better studied than GABA_A receptors.
D) exert excitatory effects on cyclic AMP.

Question 48

GABA_B receptors are unusual because unlike other metabotropic receptors, they

A) require glycine as a co-agonist.
B) require two different subunits to work properly.
C) simultaneously enhance Na⁺ channel opening and inhibit cAMP.
D) act as autoreceptors.

Question 49

GABA_B receptor agonists are clinically useful for treating

A) anxiety.
B) seizures.
C) muscle spasms.
D) alcoholism.

Question 50

Describe the role of transporters and astrocytes in the clearance, metabolism, and synthesis of glutamate (GLU) and GABA.

Question 51

Name the three ionotropic glutamate receptors in the brain. For each, identify the ions that move to create the depolarizing effects. What effect does the drug NBQX have on these receptors and on behavior?

Question 52

Describe the role of NMDA and AMPA receptors in the induction and expression phases of long-term potentiation (LTP).

Question 53

Although memantine and ketamine are thought to bind in a very similar location within the NMDA receptor channel, they have major differences and are used for different purposes. Describe the effects of these drugs and the ways they differ in terms of mode of action.

Question 54

Explain how the coincidence detection feature of NMDA receptors may allow them to play a role in associative learning.

Question 55

Distinguish between short-term excitotoxic effects of glutamate and the delayed type of programmed cell death that occurs in adult animals.

Question 56

Describe the processes by which GABA is inactivated and metabolized. Identify two drugs that affect these processes, and indicate what effect they have on behavior.

Question 57

Characterize the GABA_A receptor complex in terms of its subunits, ion channel, and the additional binding sites.

Question 58

Name one GABA_A receptor agonist and two antagonists, and compare their effects on behavior.

Question 59

What are benzodiazepines and how do they affect GABA? Why might a doctor or psychiatrist prescribe benzodiazepines?

Question 60

Describe the evidence supporting the proposal that the GABA_A receptor family that contains an α5 subunit may play a role in memory.

Question 61

Explain how the GABA_B receptor is structurally and functionally different from the GABA_A receptor.