Chapter 8: Glutamate & GABA Flashcards
Glutamate (Glu) is the main […] in the CNS.
excitatory NT
Glu is the […] form of glutamic acid.
ionized
Glutamatergic neurons use […] as an NT and are one of the most […] neural populations in the brain particularly through the […].
glutamate; abundant; cortex
Describe glutamate synthesis:
synthesized from glutamine by enzyme known as glutaminase
Is ATP required for glutamate synthesis?
yes
T/F: Glutamate can be co-expressed.
true
Dopaminergic neurons in the ventral tegmental area typically co-express…
dopamine and glutamate
What are VGLUTs?
vesicular glutamate transporters
Role of VGLUTs:
move glutamate into synaptic vesicles
VGLUTs are only found in […] neurons. This means they serve as […].
glutamatergic; genetic markers
**identify the type of neurons
List the VGLUTs types:
VGLUT1-3
VGLUT1 removed in KO mice:
survive birth but begin to die during the third week of life
VGLUT2 removed in KO mice:
die immediately after birth
VGLUT3 removed in KO mice:
viable, but completely deaf; the inner hair cells of the cochlea use glutamate as a NT
EAATs:
excitatory amino acid transporters
Roles of EAATs:
remove glutamate from the synaptic cleft
Where are EAATs located?
different locations
EAATs have a partnership with […].
astrocytes
EAATs on astrocytes mediate […]. Astrocytes convert […] into […] by […] synthetase. […] is transported out of astrocytes and back into neurons.
glutamate uptake; glutamate; glutamine; glutamine synthetase; glutamine
EAAT2 removed in KO mice:
exhibit spontaneous epileptic seizures and die after 2-3 weeks of age
List the ionotropic glutamate receptors (GluRs):
- AMPA receptors
- kainate receptors
- NMDA receptors
List the metabotropic glutamate receptors (mGlus):
Group I-III
AMPA receptors = named for the selective agonist […]
Kainate receptors = named for the selective agonist […]
NMDA = named for the agonist […]
AMPA (a synthetic AA)
kainic acid
NMDA (a synthetic AA)
Metabotropic glutamate receptors: What are the Group I receptors? Where are they located (pre/post)?
mGlu 1 and 5
mainly postsynaptic
Metabotropic glutamate receptors: What are the Group 2 receptors? Where are they located (pre/post)?
mGlu 2 & 3
mainly presynaptic
Metabotropic glutamate receptors: What are the Group 3 receptors? Where are they located (pre/post)?
mGlu 4, 6, 7, 8
mainly presynaptic
AMPA receptors are also known as…
GluR and GluA
AMPA receptors have […] subunits: GluR[…].
4; 1-4
AMPA subunits form […]. The most common ones in the adult mammalian CNS are GluA 2/3 and […].
dimers; GluA 1/2
[…] blocks AMPA and kainate, but not NMDA receptors.
NBQX
Rats treated wth NBQX exhibit sedations, […], and protection against […].
ataxia (reduced locomotion); seizures
NMDA receptors provide ion flow for both […] and […].
Na+; Ca2+
NMDA receptors are also known as …(2).
NMDA or GluN
Opening of the channel with NMDA receptors requires […] and […].
co-agonists; depolarization
What are the co-agonists that are required for NMDA receptors?
glutamate and glycine/D-serine
Depolarization at a NMDA receptor expels…
Mg2+ blockage (pore blocker)
All drugs that block the NMDA channel are […].
non-competitive agonists
Drugs of abuse that block the NMDA channel:
- PCP
- ketamine
- memantine
How many subunits for metabotropic glutamate receptors?
8
Metabotropic glutamate receptors use […] and […].
G-proteins; second messengers
Metabotropic Glu receptors: Some subunits inhibit […]. Some subunits activate […].
cAMP; IP3/DAG
Metabotropic Glu receptors: Some subunits act as pre-synaptic […] to inhibit […] release.
autoreceptors; glutamate
T/F: mGluRs are widely distributed throughout the brain.
true
Which type of drugs is being developed to treat the neuropsychiatric disorder known as fragile X syndrome?
mGluR drugs
Group I of metabotropic glutamate receptors (Gs/Gi/Gq)?
Gq
Group II of metabotropic glutamate receptors (Gs/Gi/Gq)?
Gi
Group III of metabotropic glutamate receptors (Gs/Gi/Gq)?
Gi
What is GABA?
the main inhibitory amino acid transmitter in the CNS
What is similar to GABA? How much of the spinal cord utilizes this NT?
glycine; 1/2 of the inhibitory synapses use glycine
T/F: Inhibitory NT is just as important as excitatory.
true; blocking GABA receptors results in convulsions and death
GABA synthesis occurs from the conversion of […] to GABA by the […] enzyme.
glutamate; glutamic acid decarboxylase (GAD)
Only […] neurons have GAD.
GABAergic
Can just any neuron synthesize GAD?
no only GABAergic neurons can
Drugs that affect GABA synthesis typically block […].
GAD
Drugs that block GAD:
- allyglycine
- thiosemicarbazide
- 3-mercaptopropionic acid
What are VGATs?
vesicular GABA transporters
What is the role of VGATs?
transporters to move GABA into vesicles
What are some other names for VGATs?
VIAATs (vesicular inhibitory amino acid transporters)
**they also transport glycine
What are GATs?
GABA transporters
What is the role of GATs?
transporters to remove GABA from the synaptic cleft
What is one drug that affects GATs?
tiagabine
Tiagabine affects GATs by… it results in…
selectively inhibiting GAT-1
this elevates the EC GABA
Tigabine is marketed as […] for treating […].
Gabitirl; epilepsy
GABA-T stands for…
GABA aminotransferase
GABA-T […] GABA back to […] (and succinate) in GABAergic neurons and astrocytes.
metabolizes; glutamate
What is the name of the drug that affects GABA-T?
Vigabatrin (Sabril)
Viagabatrin is a […] of GABA-T that prevents GABA […]. Build up of GABA levels in the brain has […] effects, thus, it is used to treat forms of […].
irreversible inhibitor; metabolism; anticonvulsant; epilepsy
GABA can be coreleased by many neuron types, including those that produce… (6)
- ACh
- DA
- SOM, SST
- PV
- CCK
- VIP
etc.
T/F: Populations of neurons co-release GABA and glutamate.
true SOME populations can
Co-releasing GABA and glutamate can allow […] of postsynaptic responses.
fine-tuning
How much (%) of cortical neurons use GABA as a NT?
10-20%
How much (%) of the hippocampus neurons are GABAergic?
10-40%
Hippocampus is important for […].
memory function
How much (%) of the substantia nigra neurons are GABAergic?
40-60%
Substantia Nigra is the…
midbrain DA center
Locations where GABA is found:
- cortex
- hippocampus
- substantia nigra
- basal ganglia
- micro/macro circuits
Microcircuits are […] brain regions while macrocircuits are […] brain regions.
within; between
GABAergic neurons of the striatum (STR) project to the […] and […].
globus pallidus (GP); substantia nigra (SN)
When […] input to the stratum is damaged in Parkinson’s disease, the result is abnormal firing of striatal GABAergic neurons.
DA
GABAa receptors are…
ionotropic
GABAa channels allow […] ions into neurons. This causes […] and […] of postsynaptic cells.
Cl-; hyperpolarization; inhibition
Each GABAa receptor has […] subunits of four types.
5
GABAb receptors are…
metabotropic
GABAb receptors require […] subunits to assemble in the membrane.
2
GABAb receptors have inhibitory effects on postsynaptic cells by inhibiting […] and […] opening.
cAMP; K+ channel
A classic agonist for GABAa is […].
muscimol
[…] is a competitive antagonist for GABAa receptors.
Bicuculline
Bicuculline is a competitive antagonist for GABAa receptor. It […] the binding site and has potent […] effects.
blocks; convulsant
GABAa reacts to CNS […] drugs.
depressant
Barbituates, benzodiazepines, ethanol and GABAa:
potentiating the effects of GABA NT on GABAa receptors
**positive allosteric modulation
Agonist for GABAb receptor:
baclofen
Antagonists for GABAb receptors:
Are they competitive?
saclofen and 2-hydroxysaclofen
yes
Functions of GABAb in the CNS
- learning and memory
- anxiety-like behaviors
- depression-like behaviors
- responses to drugs of abuse