Glutamate

Glutamate is classified as an _________ NT

Amino Acid

Glutamate is the more common ________ (depolarizing) NT

Excitatory

What is the conversion synthesis for neurons that use glutamate as a NT?

Glutamine —> Glutamate using Glutaminase

Since we cannot see Glutamate in neurons, how can we know a neuron is a Glutamatergic neuron?

VGLUT, EAAT, and Glutamate Receptors

Transport Glutamate into and out of the cell

VGLUT1-3 and EAAT1-3

_____ transport glutamate to Astrocytes where they are recycled

EAAT 1 and 2

Safer to convert glutamate into ________ in the astrocyte because glutamate is easily ________ so it is safe to store glutamate in its original form.

glutamine, excitable

______________ have a depolarizing effect via influx of Na+, K+, and Ca+

Ionotropic Glutamate Receptors

AMPA receptors are _______ (depolarization) and require ______ binding

ionotropic, glutamate

__________ of these AMPA (ionotropic or depolarizing receptors) is a target for anti-seizure meds (to decrease excitation) of the neuron

Antagonism

NMDA receptors are ______ (depolarization) and require _____________ and either ______ or _______

Ionotropic, Co-binding of Glutamate, Glycine, D-serine

Some drugs require the NMDA receptor to open first before binding inside the pore, what is a drug that is an example of this concept?

Ketamine

Ion channel and receptor are on the same protein

Ion Receptors

Ion channel and receptor are on different proteins, need a 2nd messenger

Metabolic Receptors

mGluR1 is _______ and ________

postsynaptic, excitatory

mGlu2-3 are _________ and _________

presynaptic, inhibitory

Neurons can build stronger connections (synaptic strengthening) so that the receiving neuron is more easily excitable than it was before - this is mediated via glutamate receptors

Long Term Potentiation

Learning and memory is especially dependent on _____ and ______ receptors

AMPA, NMDA

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using _____ and ______ receptors

AMPA, NMDA

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for ____ influx

Na+

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for Na+ influx

4. _________ and ________ do not allow NMDA channel to open for influx of Mg2+

Glutamate, co-agonist (glycine or d-serine)

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for Na+ influx

4. Glutamate and co-agonist (glycine or d-serine) do not allow NMDA channel to open for influx of Mg2+

5. __________ - high levels of simulation

Tetanus

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for Na+ influx

4. Glutamate and co-agonist (glycine or d-serine) do not allow NMDA channel to open for influx of Mg2+

5. Tetanus - high levels of simulation

6. ______ glutamate is released from presynaptic neuron

More

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for Na+ influx

4. Glutamate and co-agonist (glycine or d-serine) do not allow NMDA channel to open for influx of Mg2+

5. Tetanus - high levels of simulation

6. More glutamate is released from presynaptic neuron

7. More glutamate and co-agonist bind to ______ allowing more Na+ influx

AMPA

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for Na+ influx

4. Glutamate and co-agonist (glycine or d-serine) do not allow NMDA channel to open for influx of Mg2+

5. Tetanus - high levels of simulation

6. More glutamate is released from presynaptic neuron

7. More glutamate and co-agonist bind to AMPA allowing more Na+ influx

8. Na+ influx through AMPA causes _______ charge on Na+ and Mg2+ to allow Mg2+ to flow ___ of the cell and ____ the NMDA receptor channel

positive, out, open

LTP

1. Glutamate in vesicles being released into the synapse

2. Bind to the synapse using AMPA and NMDA receptors

3. Upon binding to AMPA, passage opens for Na+ influx

4. Glutamate and co-agonist (glycine or d-serine) do not allow NMDA channel to open for influx of Mg2+

5. Tetanus - high levels of simulation

6. More glutamate is released from presynaptic neuron

7. More glutamate and co-agonist bind to AMPA allowing more Na+ influx

8. Na+ influx through AMPA causes positive charge on Na+ and Mg2+ to allow Mg2+ to flow out of the cell and open the NMDA receptor channel

9. ____ comes through the NMDA receptor channel, causing increase in _______ receptors, more ____, and faster depolarization with _____ plug release in NMDA receptors

Ca2+, AMPA, Na+, Mg2+

Why does having Ca2+ in the postsynaptic membrane matter?

Phosphorylation of AMPA to increase Na+ influx

What happens if there is Na+ increase in the postsynaptic cell?

Cell becomes depolarized and forced Mg2+ out of the cell by opening NMDA channels

Ca2+ uses retrograde signaling to tell the presynaptic neuron to release more _________ in order to get more Na+ into the cell

glutamate

Stimulating the perforant pathway with tetanus (high frequency excitable signals) will cause LTP in the __________________

dentate gyrus of the hippocampus

What are the 3 requirements for LTP?

1. Presynaptic cell needs to be excitatory

2. Postsynaptic cell needs to have AMPA and NDMA receptors

3. Co-stimulation- presynaptic cell fires before postsynaptic cell

In Pavlovian conditioning ________ neurons receive information from interneurons of the _______ cortex and __________ cortex for LTP

amygdala, auditory, somatosensory

After pavlovian conditioning training, the ____ alone can activate the LA neuron (postsynaptic neuron) allowing _______ stimulation

CS, tetanus

When the CS and US sensory information occur in close time, then neurons in the LA experience _______

LTP

What makes glutamate receptors good targets for development of cognitive enhanacement?

Excitotoxicity

________ antagonists at low doses can decrease excitation effects of NMDA receptors

Glycine-site

Too much glutamate can cause a ______ or block of blood flow in the brain to allow glutamate to release and spread.

stroke