AMPA, NMDA and Kainate receptors are all types of what?

Glutamate receptors

Synaptic plasticity depends on what?

Intracellular signal transduction systems

What is VGLUT and where is it found?

VGLUT is the best marker of glutametergic neurons and is found spanning the vesicular membrane in presynaptic terminals

What role do glial cells play in the glutamate cycle?

Through EATT, they take in glutamate that has been released by the neurotransmitter and convert it to glutamine with glutamine synthetase; this glutamine gets sent back to the terminal and converted back to glutamate with glutaminase

What part of the brain is essential for forming spatial memories?

The hippocampus

What did O'Keefe and Dostrovsky show in their 1971 study on rats that traveled through different spatial areas?

Hippocampus neuronal firing was very rapid when the mouse was in favorable fields that contained some sort of positive stimulus

How do different cells in the hippocampus encode spatial memory?

They encode different places in the overall spatial field; the shape and size of firing fields can be very different from one cell to another

1. Entorhinal cortex -> perforant path -> denate gyrus granule cells 2. Denate gyrus granule cells -> CA3 pyramidal cells 3. CA3 cell Schaffer collaterals -> CA1 pryamidal cells

What happens when high-frequency stimulation is applied to a synapse in the hippocampus?

That synapse greatly increases in membrane voltage upon firing after treatment; this is referred to as "synaptic memory"

CA3 -> CA1 synapses can undergo what?

Long term potentiation

With high frequency stimulation in the hippocampus, you can certainly depolarize the postsynaptic neuron, but what else can you also do?

You can also depolarize the presynaptic neuron as it becomes conditioned to firing so regularly

What is one potential side effect of high frequency stimulation of hippocampal cells?

There is potential for long-term depression of hippocampal cells with regard to their EPSP amplitude

The gating (glutamate only) and conductance (Na/K) are similarities between what two receptor types: AMPA, NMDA or kainate?

AMPA and kainate

These two ionotrphic glutamate receptors both have relatively high expression levels in the brain and are primarily involved in synaptic signaling; choice between AMPA, NMDA and kainate receptors

AMPA and NMDA receptors

This receptor type is both ligand and voltage dependent (depolarization is needed to remove the magnesium block), requires co-activation by 2 ligands (glutamate and glycine), has Na, K and Ca conductance and has a VERY strong affinity for glutamate

NMDA receptors

How are AMPA receptors gated?

Only by glutamate binding

What are NMDA receptors gated by?

They are gated by both glutamate binding and by depolarization

Glutamate released from presynaptic action potentials trigger small EPSPs, but why not big EPSPs?

Glutamate release only opens AMPA receptors, not NMDA receptors

What is one way in which glutamate receptors are similar to nicotinic acetylcholine receptors?

They have a very similar voltage-current relationship

How do AMPA-Rs function when glutamate is bound?

They quickly open their ion channel but a second conformational change then closes the channel while glutamate is still bound

At resting potential, the pore of NMDA receptors is blocked by magnesium ions. What causes them to dissociate from the channel?

Membrane depolarization

What is interesting to note about the total EPSP from L2/3 cortical pyramidal neurons with regards to the AMPA-R and NMDA-R components?

The AMPA-R portion of the signal accounts for most of the signal in the EPSP

What is important to note about the activation of NMDA receptors?

Their activation causes calcium entry into dendritic spines of CA1 pyramidal neurons

What does calcium entry into neurons cause in NMDA-Rs?

It causes desensitization (inactivation). The amount of inward current gets progressively smaller but can recover under low calcium conditions

What effect can (de)phosphorylation of intracellular components of the NMDA receptor have?

Dephosphorylation can decrease NMDA receptor currents while phosphorylation has the opposite effect

Why is it said that the NMDA-R acts as a "coincidence detector"?

It only opens when there is simultaneous pre and post synaptic activity

What happens to the resulting EPSP when NDMA-Rs are activated due to paired-pulse stimulation?

It is significantly greater than expected

Hebb's postulate says that coordinated activity of pre and post synaptic neurons (blank) the synapse

Strengthen

How does calcium influx create long-lasting changes in the AMPA receptors?

Calcium influx activates CaM kinase II which phosphorylates AMPA receptors; this directly leads to increased permeability of sodium in AMPA receptors and that leads to larger EPSPs

What is calmodulin (CaM) and why is it so important?

It is a ubiquitous intracellular calcium receptor with 4 calcium binding sites. It activates many proteins which include cytoplasmic and membrane proteins

Phosphorylation of existing AMPA-Rs, new AMPA-Rs inserted into the postsynaptic membrane and the dissociation of NMDA receptors from the cytoskeleton (which causes a conformational change in the receptor leading to inactivation) are all caused by what?

Calcium influx that activates calmodium and CaM kinase II

What happens when you stimulate hippocampal synapses with 100 vs 1 Hz frequencies?

100 Hz will generate long-term potentiation while 1 Hz stimulation will generate long-term depression of the EPSP signal

What happens to AMPA receptors in the case of long-term depression in synapses?

They become internalized in the postsynaptic bud