NRSC4032 - Chapter 10: Memory Formation: Early Stages

Roberto Malinow's laboratory (Rumpel et al., 2006) used two strategies to prove that fear conditioning drives AMPA receptors into amygdala neuron synapses. What were they?

1) In one case, he created identifiable GluA1 receptors and infected neurons in the amygdala with these receptors to show that fear conditioning would drive them into synapses. 2) He created dummy receptors to compete with endogenous receptors and showed that their presence impaired fear conditioning

Describe how the radial arm maze can be used to study both working and reference memory.

1) Working memory requires that the animal remember which arm was already visited 2) reference memory requires that the animal discriminate between the arms always baited and the arms never baited.

Which strategies did Malinow's laboratory use to the role of AMPA receptors in memory formation?

1.) he used a virus to delivery dummy AMPA receptors to the amygdala 2.) he used a virus to deliver artificial AMPA receptors to the amygdala 3.) he used a fear conditioning procedure

In Malinow's AMPA receptor trafficking experiment, what was the difference between the rats in the paired condition and the rats in the unpaired condition?

After the training, rats in the paired condition had more GluA1 receptors in the plasma membrane than rats in the unpaired condition.

Why would infant mice display stronger LTP than older mice?

Because the ratio of GluN1-GluN2B to GluN1-GluN2A receptor complexes is higher in the infant mice, and GluN1-GluN2B receptor pass more calcium.

What are ampakines?

Drugs that enhance AMPA mediated depolarization by slowing the inactivation of the AMPA channels.

Describe the composition of the NMDA receptor.

Each receptor has four subunits, and they are some combination of the two classes GluN1 and GluN2.

Every functional NMDA receptor has __________ subunits.

GluN1

Tonegawa deleted the __________ in __________ in the CA1 field of the mouse hippocampus.

GluN1 subunit; pyramidal cells

he Doogie mouse is genetically engineered to overexpress __________ subunits.

GluN2B

As the nervous system develops, __________ subunits tend to be replaced by __________ subunits.

GluN2B; GluN2A

When __________ subunits dominate, it is easier to induce LTP than when __________ subunits dominate.

GluN2B; GluN2A

Morris was the first to find a possible role for NMDA receptors in memory formation. What was his essentially methodology?

He implanted a cannular into a ventricle to delivery an NMDA receptor antagonist. He assessed the effect by studying its effect on the hidden platform version of the water task.

Provide an example of working memory.

Memorizing a list of groceries and discarding it from your memory once you are done shopping.

Richard Morris was the first researcher to directly investigate the role of __________ in memory formation.

NMDA receptors

Explain why it is possible to induce LTP in the dentate gyrus of the CA1KO mouse, but not in the CA1 region of the brain. How does this affect the mouse's performance in the place-learning task?

The genetically engineered deletion targeted the NMDA receptors in CA1 pyramidal cells but not the dentate gyrus. The mouse's memory was impaired, and it could not learn to swim to the platform.

How did Tonegawa's laboratory discover a role for the GluN1 receptor?

They deleted the gene for this receptor in the CA1 region in mice and found that it impaired performance in the hidden platform task.

Is it reasonable to expect that behavioral experiences that produce memories would engage the LIMK signaling pathway? Why?

Yes, because actin polymerization is necessary for synaptic changes in LTP.

Fear conditioning increased the presence of phosphorylated CaMKII in dendritic spines. This result means that the conditioning experience __________ this __________.

activated; kinase

The __________ of __________ may be critical for the rapid formation of a memory, but other processes can compensate for this contribution when multiple training trials occur.

autophosphorylation; CaMKII

The formation of a memory trace begins when a __________ activates a set of __________ neurons.

behavioral experience; weakly connected

Ampakines cross the __________ and bind to a site on the __________ receptor.

blood-brain barrier; AMPA

(T/F) AMPA receptors are needed only for memory acquisition, but NMDA receptors are required for both acquisition and retrieval.

false

(T/F) Early in development, the ratio of NR1/NR2B to NR1/NR2A containing NMDA receptors favors the NR1/NR2A complex.

false

(T/F) GluN1-GluN2A receptor complexes influx more calcium than GluN1-GluN2B receptor complexes.

false

(T/F) GluN1-GluN2B receptors to GluN1-GluN2A ratio increases during development

false

(T/F) Morris used genetically engineered mice in the first study that investigated the role of NMDA receptors in memory formation.

false

(T/F) NMDA receptors are required for both the acquisition and the retrieval of memories

false

(T/F) Remembering the plot of a book you read a few months ago is an example of working memory.

false

(T/F) The CA1KO mouse was able to display LTP in the CA1 regions but not in the dentate gyrus.

false

(T/F) The Doogie mouse was engineered to overexpress GluN2A receptors.

false

(T/F) Working memory cannot be studied in animals because they cannot communicate what problems they are trying to solve.

false

Malinow's experiments showed that memory for the fear experience, as measured by the rat's __________, depends on trafficking AMPA receptors with __________ into the membrane.

freezing response; functional GluA1 subunits

What supports the hypothesis that CaMKII is important for memory formation?

genetically deleting CaMKII prevents acquisition, and preventing autophosphorylation of CaMKII interferes with one trial learning.

To influence NMDA function, Morris

infused APV into the brain and tested rats in the space-learning swim task

When glutamate and ampakines both bind to the AMPA receptor, the channel stays open __________.

longer

If the GluA1 is deleted reference memory in the radial maze will be _______?

normal

Deleting the GluA1 subunit ______ working memory but has _____ effect of reference memory

prevents; no

In the radial arm maze methodology, if a rat revisits an arm that was never baited, it is making an __________ error.

reference memory

(T/F) AMPA receptors are important in both the induction and expression of LTP.

true

(T/F) Ampakines are an example of a receptor modulator.

true

(T/F) Ampakines are neither agonists nor antagonists.

true

(T/F) An important step in the generation of a memory is the release of glutamate onto dendritic spines.

true

(T/F) GluA1 KO mice display long lasting LTP, but show impaired working memory

true

(T/F) GluN1 subunits are absent in the CA1 region of the CA1KO mouse

true

(T/F) GluN1 subunits are necessary to form functional NMDA receptors.

true

(T/F) LTP can be induced in the dentate gyrus in the CA1KO mouse

true

(T/F) Morris used a pharmacological treatment to study the role of NMDA receptors in memory formation.

true

(T/F) NMDA receptor channels allow calcium to enter the cell.

true

(T/F) NMDA receptors are important in the induction, but not the expression, of LTP.

true

(T/F) The CA1KO mouse was able to display LTP in the dentate gyrus region but not in the CA1.

true

(T/F) The Doogie mouse was engineered to overexpress GluN2B receptors.

true

(T/F) The formation of a memory trace begins when a behavioral experience activates a neuronal ensemble that represents the experience.

true

(T/F)A behavioral experience that produces a memory is likely to result in more phosphorylated cofilin and more autophosphorylated CaMKII.

true

In the radial arm maze methodology, if a rat revisits an arm, it is making an __________ error.

working memory