Ch. 10: Early Stages of Memory Formation

In the radial methodology maze task, A) Rats rarely make reference or working memory errors. B) Rats make reference memory errors but not working memory errors. C) Rats make working memory errors but not reference memory errors. D) Rats make both types of errors equally. E) None of the above.

A

The Doggie mouse is genetically engineered to overexpress _________ subunits. A) GluN2A subunits B) GluN2B subunits C) GluN2C subunits D) GluN1 subunits E) Both B and D

B

Which of the following is true? A) NMDA receptors are activated by calcium B) NMDA receptor channels allow calcium to enter the cell C) NMDA composed of the NR1/NR2A subunits remain open longer than those composed of NR1/NR2B subunits. D) Early in development the ratio of NR1/NR2B to NR1/NR2A containing NMDA receptors favors the NR1/NR2A complex

B

Which of the following statements about NMDA receptors is true? A) NMDA receptors are activated by calcium. B) NMDA receptor channels allow calcium to enter the cell. C) NMDA receptor channels allow calcium to enter the cell. D) Early in development the ratio of GluN1/GluN2 subunits remain open longer than those composed of NR1/NR2B subunits. E) None of the above are true.

B

GluA1 KO mice A) Display short-lasting LTP. B) Display long-lasting LTP C) Have impaired working memory. D) have impaired reference memory E) Both B and C

E

To influence NMDA function, Morris: A) Used a pharmacological approach. B) Infused APV into the brain. C) Tested rats in the space-learning swim task. D) Implanted a cannula into a cerebral ventricle. E) All of the above

E

Which of the following statements about LTP is true? A) AMPA receptors have been shown to be important in both the induction and expression of LTP B) NMDA receptors have been shown to be important in both the induction and expression of LTP C) AMPA receptors have been shown to be important in the induction but not the expression of LTP D) NMDA receptors have been shown to be important in the induction but not the expression of LTP E) Both A and D

E

which of the following statements about the CA1KO mouse is true? A) GluN1 subunits are absent in the dentate gyrus. B) GluN1 subunits are absent in the CA1 region. C) LTP cannot be induced in CA1 in slices D) LTP cannot be induced in the dentate gyrus E) Both B and D

E

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

False

T/F GluN1 subunits are not required to form functional NMDA receptors.

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 the dentate gyrus.

False

T/F Working memory cannot be studied in animals, because they cannot communicate when problems they are trying to solve.

False

Every functional NMDA receptor has _________ subunits.

GluN1

Which receptor subunit is required to form a functional receptor?

GluN1

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

What was Richard Morris' experiment? What was he trying to study?

He implanted a cannula to deliver the NMDA receptor antagonist APV into the ventricular system of a rat's brain where it would enter the cerebral spinal fluid. He was testing the hypothesis that the initial formation of a memory trace depends on the activation of NMDA receptors.

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

NMDA receptors

T/F A behavioral experience that produces a memory is likely to result in more phosphorylated cofilin and more autophosphorylated CaMK2.

True

T/F Ampakines are neither antagonists nor agonists.

True

T/F An enduring LTP can be estimated independent of any contribution from GluA1 receptors, but it requires GluA2 AMPA receptors

True

T/F Memory formation can take place without the contribution of NMDA receptors.

True

T/F Morris used genetically engineered mice in the first study investigating the role of NMDA receptors in memory formation.

True

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

True

Fear conditioning increased the presence of phosphorylated CaMK2 in dendritic spines. This result means that the conditioning experience _________ this _________.

activated this kinase

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 trafficked into the plasma membrane than rats in the unpaired condition.

Wha are ampakines?

ampakines bind to a site on AMPA receptors and increase the duration of the channel opening when glutamate also binds to the receptor.

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, CaMK2

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

behavioral experience, weakly connected

What is cerebral spinal fluid?

cerebral spinal fluid is the substance that covers the brain and spinal cord and cushions them against impact. It also provides them with oxygen and nutrients and removes waste products.

Describe the composition of the NMDA receptor.

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

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

freezing response, functional GluA1 subunits

What genetic engineering methods were used to study the role of NMDA receptors in memory formation?

genetic engineering methods have been used to selectively delete or overexpress one of the NMDA subunits in mice.

Roberto Malinow used two strategies to prove that fear conditioning drives AMPA receptors to amygdala neuron synapses. What were they?

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

If there are more GluN1-GluN2B receptor complexes present in a tissue sample than GluN1-GluN2A receptor complexes, what was the likely age of the mouse?

it is likely a sample from a very young animal, because with maturation the composition of NMDA receptors changes, and GluN2-GluN2B receptor complexes are replaced by GluN1-GluN2A receptor complexes.

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

longer

Provide an example of working memory.

memorizing a list of groceries and discarding the list from your memory once you are done shopping.

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

reference memory

The _________ of AMPA and NMDA receptors determines whether or not rodents are successful on working memory and reference memory tasks.

subunit composition

What is the Dooggie mouse?

the Doogie mouse was genetically engineered to overexpress GluN2B subunits in the cortex and the hippocampus. Doogie mice displayed enhanced LTP, enhanced memory formation, and superior performance in behavioral tests.

Tonegawa deleted _________ in _________ in the Ca1 field of the mouse hippocampus.

the GluN1 subunit, pyramidal cells

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

the blood-brain barrier, AMPA

What is a reasonable conclusion that can be made based on Saucier and Cain's observations? Did they disprove the role of NMDA receptors as crucial to memory formation?

the brain has redundant mechanisms that might substitute for each other and there are such mechanisms that can produce memories when NMDA receptors are not functional. No, it is possible that functioning NMDA receptors normally contribute to creating place memories.

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 cell and not the dentate gyrus. Its memory was impaired and it could not learn to swim to the platform.

What evidence suggest that actin regulation is critical for memory formation?

the training procedure used to produce object-place recognition memory increases phosphorylated cofilin.

Defend or refute the following statement citing experimental evidence to support your argument: "GluA1 subunits are required for the initial early phase of LTP but not for the later developing phase."

this is true because, when stimulated by a stronger theta-burst protocol, slices from the GluA1 of KO mice display an enduring LTP equivalent to control mice, even though they do not display the early, short-lasting phase.

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

working memory

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

working memory requires the animal to remember which arm was already visited, and reference memory requires the animal to discriminate between the arms always baited and the arms never baited.

As the nervous system develops, would you expect to see any changes in LTP induction? Explain why or why not.

yes because GluN2B subunits are replaced by GluN2A subunits and they have different channel-opening properties. NMDA receptors complexes that contain GluN2B subunits remain open longer than those that contain GluN2A subunits and presumably permit more Ca2+ to enter the spine. When the GluN2B subunits dominate, it is easier to induce LTP than when GluN2A subunits dominate.

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

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