Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PSYCH 478 > InInhibitory Neurotransmission: GABA and Glycine > Flashcards

InInhibitory Neurotransmission: GABA and Glycine Flashcards

1
Q

What is the main inhibitory NT in the CNS and where can it be found?

A

GABA and 10-40% is found in the cortex, hippocampus and substantia nigra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does GABA increase the conductance of?

A

Chloride ions across cell membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

True or false: Glycine has comparable but limited functions as an inhibitory NT

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the synthesis of GABA?

A

Glutamate————–> GABA
GAD
GAD- glutamic acid decarboxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

True or false: GABA and glycine do not share a vesicular transporter

A

False; they do share transporters and they are VGAT or IAAT (inhibitory amino acid transporter)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does VGAT identify

A

Both GABAergic and glycinergic neurons in the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is one antagonist of GAD that is used experimentally

A

Allyglycine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does inhibition of GAD do and drugs that decrease GABAergic activity are limited to what?

A

Inhibition of GAD decreases GABA levels and leads to convulsive activity

GABAergic activity is limited in use to in vitro studies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where are GABA transporters (GAT) located

A

GAT are found on astrocyte and neuronal membranes at the synapse

GAT-1 is located on neurons and astrocytes

GAT-2 and 3 are principally astrocytic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Review slide 7 for metabolism and neuronal synthesis

A

memorize that shit like your life depends on it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Drugs that increase GABA activity are

A

Anticonvulsants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Tiagabine is a selective antagonist of what

A

GAT-1 and elevates GABA levels in synapse, tiagabine is approved as an adjunctive AED for epilepsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

________ is an irreversible inhibitor of GABA-T and elevates GABA levels in the brain by blocking breakdown

A

Vigabatrin, also approved as an AED for epilepsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

True or false: GABA is widely used in inhibitory interneurons throughout the brain

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does chandelier cells synapse onto and the cells of the cortex are

A

Onto the axonal initial segments of pyramidal cells

cells of the cortex are GABAergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

in addition to axo-dentritic synapses GABA-ergic synapses are often what?

A

axo-somatic-> synapses that control excitability of cell body

axo-axonal-> synapses at the axon inital segment influence signal integration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what cells are large GABAergic projection neurons of the cerebellum and provides the sole output of motor coordination from the cerebellar cortex

A

purkinje cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

True or false: purkinje cells are under inhibitory control from GABAergic interneurons

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is the term for degeneration of purkinje neurons and what are the side effects

A

Holmes cerebellar degeneration-> impaired fine hand movements, speech deficits, tremors and ataxia while walking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the difference between the direct pathway and the indirect pathway that controls the initiation of motor activity in the basal ganglia

A

direct pathway-> excitatory input from cortex causes excitation of upper motor neurons in motor cortex

indirect pathway-> excitatory input from cortex causes inhibition of upper motor neurons in motor cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what kind of neurons comprises 90-95% in the striatum

A

medium spiny

input from neocortex (all except visual and auditory)

outputs to global pallidus and substantia nigra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Review slide 13 and 14 for reference on how the pathways carry out their functions

A

be able to draw the output of one another

everything starts with cortical input*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what are the disinhibit outputs of the direct pathway

A

VTh- excitatory projections to upper motor neurons of cortex

superior colliculus- controlling eye saccades

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

activation of what area of dopamine promote the direct pathway (d1- excitatory) over the indirect pathway (D2-inhibitory)

A

nigrostriatal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

true or false: cholinergic interneurons act directly on the indirect pathway

A

false; direct pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what antagonists and inhibitors are useful in therapeutics in early parkinson’s as they compensate for decreased dopaminergic input

A

M4AChR antagonists and AChE inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what are the two classes of GABA receptors

A

ionotropic (GABA(A))

metabotropic (GABA(B))

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is ionotropic responsible for

A

classic ligand gated ion channel permeable to Cl-

5 subunits form the channel pore

originally characterized by sensitivity to bicuccline (antagonist)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is metabotropic responsible for

A

g-protein coupled receptors

Gi- ihibits adenylate cyclase (decrease cAMP)

Gby- opens G-protein coupled K+ channel

originally characterized by sensitivity to baclofen (specific agonist)

30
Q

True or false: GABA has 4 binding sites for endogenous and exogenous ligands

A

true

31
Q

what are the four sites

A

GABA site-> binds two molecules of GABA at the interface between a and b subunits

benzodiazepine site- binds benz (tranquilizers) as positive allosteric modulators

barbiturate site-> binds barb (sedative and anxiolytic) as positive allosteric modulators

neurosteroid site-> binds endogenous neurosteroids as positive allosteric modulators

32
Q

what is picrotoxin

A

a non-competitive channel blocker

33
Q

what binds in the pores at the same sites as picrotoxin in the non-competitive sites that was used as convulsants for depression therapy

A

pentylenetetrazol-> discontinued due to high risk of spontaneous seizures

34
Q

what is the competitive antagonist in the GABA sites

A

bicucculine-> widely used in animals models of epilepsy

35
Q

what is a classical agonist of GABA sites

A

muscimol

36
Q

what does consumption of fly agaric lead to

A

serious side effects due to the muscarinic cholinergic effects at NMJ and parasympathomimetic effects

37
Q

what is the synthetic version of muscimil with reduced psychotropic effects

A

gaboxidol

investigated for insomnia treatment

38
Q

true or false: barbiturates has a higher safety margin than benzodiazepines

A

false: benzodiazepines has a higher safety margin

39
Q

what is a well known benzodiazepines

A

diazepam

40
Q

binding of benzodiazepines causes ________ probability of pore opening

A

increased

41
Q

high risk of drug interactions of benzodiazepines at the ___________ _____________

A

GABA(A) receptors

42
Q

what is a best known barbiturates

A

phenobarbitol

43
Q

what happens when barbiturates bind

A

prolongs open time of Cl- pore

44
Q

where are barbiturates used

A

used in physician-assisted suicide and euthanasia

45
Q

what is another term for sodium amytal

A

truth serum

46
Q

what is a potent positive allosteric modulator of GABA(A) binding to a sie on the transmembrane surface

A

ethanol

47
Q

what may ethanol exert

A

sedative, euphoric, and addictive effects through modulation of GABA(A)

48
Q

True or false: ethanol binds GABA(A) with very low affinity- binding even at doeses that would be considered moderate

A

false: very high affinity

49
Q

_______ is a potent anaesthetic that interacts with the transmembrane surface of the b-subunit of GABA(A)

A

propofol-> positive allosteric modulator that increases channel open time

50
Q

how many subunits of GABA(A) channels

A

5- subunits:
6 α (GABARA1-6)

3 β (GABARB1-3)

3 γ (GABARG1-3)

One each of δ (GABARD), ε (GABARE), θ (GABARQ), π (GABARP)

3 ρ (GABARR)*

51
Q

what is the special case for GABA(A)

A

GABA(A)P which only forms homopentameric channels with itself

52
Q

what is a normal channel form

A

atleast 1 each of a,b
most common is a2b2y

53
Q

What is an orphan receptor site? What are the proposed ligands?

A
  • receptor site where endogenous ligand is not known
  • proposed ligands: inosine, diazepam binding inhibitor/acyl-CoA binding protein, endozepines
54
Q

Which drug is associated with orphan receptor site?

A

benzodiazepines

55
Q

GABAb receptors primarily affect _______ by coupling _________.

A

excitability; GIRK

56
Q

Describe GIRK activation. Is it inhibitory or excitatory?

A
  • inhibitory
  • K+ efflux –> hyperpolarize
57
Q

While GABAa is repsonsible for _____, ___ IPSP, GABAb/GIRK is responsible for _____, ______ IPSP.

A
  • GABAa = fast, weak
  • GABAb = slow, strong
58
Q

What is the reversal potential of Cl- and K+? Which GABA receptors are these ions associated with?

A
  • GABAa –> Cl- = -70mV
  • GABAb –> K+ = -90 mV
59
Q

What is baclofen?

A
  • specific agonist of GABAb
  • muscle relaxant
  • antispastic
60
Q

What is γ-hydroxybutyric acid (GHB)? When is it excitatory/inhibitory?

A
  • weak GABAb agonist
  • excite at GHB receptor at low dose –> recreational
  • inhibit at GABAb receptor at high does –> date rape drug
61
Q

Describe GIRK signaling in detail.

A
  • K+ channel activated during GPCR signalling
  • GIRK opens on binding of Gβγ
  • K+ exits the cell causing hyperpolarization of the cell membrane
  • GIRK signalling inhibits subsequent depolarizing stimuli
62
Q

GABAa-rho receptor is insenstive to? more sensitive to? lack binding sites for?

A
  • insensitive to: baclofen, bicucculine
  • more sensitive to: GABA
  • lack binding sites for: benzodiazepines, barbiturates, neurosteroids
63
Q

Where are GABAa-rho receptors found? what kind of signals and from what cells does it receive?

A
  • bipolar cells of retina
  • inhibitory signals from amacrine and horizontal cells
64
Q

mutations in GABAa-rho are assocaited with hertiable cases of ______________.

A

retinites pigmentosa

65
Q

GABA development in the ________ is a late developmental step and is associated with maturation of ____________, _____________, and _____________.

A

PFC; impulse control, working memory, and executive function

66
Q

How is GABA related to anxiety? What are the possible models?

A

GABA agonists and positive allosteric modulators are ANXIOLYTIC
1. anxiety caused by secretion of endogenous INVERSE agonists of GABAR –> inhibitor of GABAR increase anxiety?
2. ligand activity at GABAR is shifted in anxiety –> subunit alteration?
3. secretion of endogenous agonists of BENZODIAZEPINE site during stress –> deficit in anxiety disorders?

67
Q

How is development related to GABA?

A
  • high levels of GABA and developmental chagnes (Excite/inhibit switch) in GABA activity
  • GABA –> cell proliferation, survival, motility
  • excitatory/inhibitory balance –> normal brain development
68
Q

WHat is an example of E/I imbalance in conditions? these conditions have a higher risk for what disorder?

A
  • down syndrome; autism
  • high risk of seizure disorder
69
Q

How is epilepsy related to GABA? How do drugs that increase/decrease GABA relate?

A
  • E/I balance in seizure disorders
  • drugs that decrease GABA/inhibit GABAR –> convulsant
  • drugs that increase GABA/increase GABAR fxn –> anticonvulsant
70
Q

How are psychiatric disorders related to GABA?

A

contribute to hyperactivity through decreased inhibitory signaling

PSYCH 478 (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions