Excitatory Amino Acid Transmitters Flashcards
What is the primary neurotransmitter released by glutamatergic neurons?
Glutamate
What are Excitatory Amino Acids (EAAs)?
A group of excitatory neurotransmitters including
- glutamate
- aspartate
- cystate
- homocystate
Which EAA do most excitatory receptors release?
The majority release glutamate
Do glutamatergic neurons respect Dale’s law?
No, some dopamine neurons can also release glutamate
Why are EAAs the most abundant chemicals in the brain?
Because they are the main excitatory input in the brain
Describe glutamate synthesis?
- Krebbs cycle produces glucose > 2. glucose is brought into the vesicle via vesicular glutamate transporter (which is a proton anti-transporter, bringing 1 glu in for every 1 H+ out) > after glutamate is released, surrounding astrocytes terminate the signal via EAAT; astrocyte stores glutamate >4. astrocyte modifies glutamate to glutamine via glutamine synthase (when glucose is low, glutamine is lent to neuron via system A transporter >5. when it’s time to make more glutamate, glutamine is transformed back into glutamate via glutaminase
What are the four EAA receptors?
- NMDA
- AMPA
- Kainate
- mGluR (7 types, from mGluR1…mGluR7, barring mGluR5)
What does ischemia mean?
Lack of blood flow?
What does anoxia mean?
Lack of oxygen
What do ischemia and anoxia both lead to?
excitotoxicity
What does the term ionotropic refer to?
That the receptor is a ligand-gated receptor
What does the term metabotropic refer to?
That the receptor is a G-Protein coupled receptor
Which of the EAA receptors are ligand-gated?
NMDA, AMPA and Kainate
Which of the EAA receptors are metabotropic?
mGluR
What is an autoreceptor?
A receptor that regulates the future release of a NT
- NT binds to autoreceptor along with post-synaptic neuron, which almost always reduces NT release
Where are autoreceptors always located?
On the presynaptic neuron
Where are EAA receptors located?
Either on pre- or post-synaptic membrane
What does a glutamate autoreceptor do?
Inhibits both glutamate synthesis as well as its release
Which of the EAA receptors is glutamate an agonist for?
mGluR
- these are made up of Gq, Gi and Gnot
Describe the binding of glutamate to an AMPA receptor
- Glu binds to active site
2. Na+ and K+ flow in (therefore we can conclude that the reaction is excitatory because of Na+)
Describe the binding of glutamate to an NMDA receptor
- glutamate binds to active site
- cell membrane becomes permeable to Na+, K+ and Ca2+ (causes an enhanced or prolonged effect due to Ca2+’s second messenger cascade)
- glycine is required to bind in order to remove magnesium channel blocker
What is so special about NMDA receptors?
- They have magnesium ions sitting in the channel, because they are attracted to the negative charge on the inside of the membrane. Magnesium acts as a channel blocker (meaning that under normal -70mV conditions, no ion flow passes through the channel)
- Along with the target binding site, NMDA receptors also have binding sites for zinc, PCP, ketamine, glycine and polyamine
What do PCP drugs do?
They are channel blockers
What does long-term potentiation mean?
An increase in post-synaptic response to to increased stimulation; produces long-term change
What are the three NMDA subunits?
- NR1
- NR2
- NR3
- need a combo of these three to form pentomere (ex. NR1, NR1, NR2, NR3 or NR2, NR3, NR3, NR3, etc)
What happens in the brain when we go from a high frequency stimulation to a low frequency stimulation?
We maintain a high EPSP (it is firing at a high frequency because it was potentiated)
What is an EPSP?
Excitatory post-synaptic potential
- is the result of high stimulation
What does tetanus mean?
A high frequency stimulation
Which brain area is the seat of long-term potentiation?
The hippocampus (this is why the hippocampus is the centre of long-term memory)
How did Pavlov’s dog learn that a bell predicts food?
Because the bell was a reliable predictor of food
- the association is due to reduction of non-food signals being brought to the neuron, while potentiating the signal that is associated with food
What is another way to think about long-term potentiation?
“Cells that fire together wire together”
